Materiały źródłowe

• #1 Charcot-Marie-Tooth (CMT): Symptoms, causes, types, and treatment

  https://www.medicalnewstoday.com/articles/172056

  Charcot-Marie-Tooth disease is a genetic condition of the nerves that affects 1 in 2,500 people in the United States. […] CMT is hereditary, so people who have close family members with CMT have a higher risk of developing it. […] CMT can affect the axon, the myelin sheath, or both, depending on the type of CMT. […] Faulty, genes cause the myelin sheath to disintegrate. […] The faulty gene affects the axons directly. […] CMT X is caused by an X-chromosome mutation.

• #2 Charcot-Marie-Tooth disease (CMT) | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/charcot-marie-tooth-disease-cmt

  Charcot-Marie-Tooth disease (CMT) is an umbrella term for a range of certain inherited genetic conditions that affect the peripheral nervous system. […] CMT either interferes with the production of proteins that make up the myelin sheath, or else affects the structure or function of the axon. […] CMT is the most common inherited condition affecting the peripheral nervous system. […] Most inherited conditions can only be passed on by one or two patterns of inheritance. However, CMT can be inherited via most known patterns of inheritance and is the most common inherited condition of the peripheral nervous system. Patterns of inheritance for CMT include: autosomal dominant, autosomal recessive, and X-linked. […] The causes of the various types of CMT include: CMT Type 1A a duplicated gene on chromosome 17, CMT Type 1B a genetic change on chromosome 1, CMT Type 1C a genetic change on chromosome 16, CMT Type X-linked a genetic change on the X chromosome, CMT Type 2A a genetic change on chromosome 1, CMT Type 2B a genetic change on chromosome 3, CMT Type 2C a genetic change on chromosome 12, CMT Type 2D a genetic change on chromosome 7. […] Recently, a number of new genes have been discovered, which cause some less common forms of CMT.

• #3 Charcot-Marie-Tooth Disease | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/charcot-marie-tooth-disease

  Charcot-Marie-Tooth disease (CMT) is a group of genetic conditions that affect the nerves connecting the brain and spinal cord to the rest of the body. […] More than 100 genes are linked to CMT. Depending on the gene problem, CMT can affect the axon, the myelin sheath, or both. […] Although different forms of CMT involve mutations in different genes that produce proteins needed for the axon or myelin to work, all forms of CMT affect the function of peripheral nerves. Gene defects in myelin and the axons can cause them to stop working as they should, disrupting nerve signals and sometimes leading to nerve loss. […] CMT is mostly an inherited disorder, and people with a family history of Charcot-Marie-Tooth (CMT) disease are more likely to develop it. […] People inherit CMT gene mutations in three main ways: autosomal dominant, autosomal recessive, and X-linked.

• #4 Understanding CMT: Symptoms & Management

  https://www.cmtausa.org/understanding-cmt/what-is-cmt/

  Named after the three doctors who first described it in 1886: Charcot (shar-coh), Marie, and Tooth, Charcot-Marie-Tooth disease (CMT) is an inheritable peripheral neuropathy that includes many motor and/or sensory neuropathies, axonopathies, myelinopathies, and neuronopathies. […] CMT AFFECTS ONE IN EVERY 2,500 PEOPLE a rare disease subdivided into multiple subtypes, each with a lower prevalence. Although CMT is a rare disease, it is also the most common inherited peripheral neuropathy. […] CMTA HAS CATALOGED MORE THAN 160 INDIVIDUAL TYPES OF CMT, each caused by one of many various mutations in more than 130 genes CMTA has also cataloged. […] CMT IS INHERITED IN ONE OF FIVE DIFFERENT WAYS, and each is an inheritance pattern. CMTs five inheritance patterns are autosomal dominant, autosomal recessive, X-Linked dominant, X-Linked recessive, and one type is inherited via mitochondrial inheritance.

• #5 Charcot-Marie-Tooth Disease | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/charcot-marie-tooth-disease

  Charcot-Marie-Tooth disease (CMT) is a group of genetic conditions that affect the nerves connecting the brain and spinal cord to the rest of the body. […] More than 100 genes are linked to CMT. Depending on the gene problem, CMT can affect the axon, the myelin sheath, or both. […] Although different forms of CMT involve mutations in different genes that produce proteins needed for the axon or myelin to work, all forms of CMT affect the function of peripheral nerves. Gene defects in myelin and the axons can cause them to stop working as they should, disrupting nerve signals and sometimes leading to nerve loss. […] CMT is mostly an inherited disorder, and people with a family history of Charcot-Marie-Tooth (CMT) disease are more likely to develop it. […] People inherit CMT gene mutations in three main ways: autosomal dominant, autosomal recessive, and X-linked.

• #6 Charcot-Marie-Tooth disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/charcot-marie-tooth-disease/

  Charcot-Marie-Tooth disease can be caused by mutations in many different genes. These genes provide instructions for making proteins that are involved in the function of peripheral nerves in the feet, legs, and hands. The gene mutations that cause Charcot-Marie-Tooth disease affect the function of the proteins in ways that are not fully understood; however, they likely impair axons, which transmit nerve impulses, or affect the specialized cells that produce myelin. In most cases, longer nerves that transmit impulses to the appendages of the body are more likely to be affected. As a result, peripheral nerve cells slowly lose the ability to stimulate the muscles in the feet, legs, and eventually the hands, and to transmit sensory signals from these appendages to the brain. Different mutations within a single gene may cause signs and symptoms of differing severities or lead to different types of Charcot-Marie-Tooth disease.

• #7 Charcot-Marie-Tooth disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/charcot-marie-tooth-disease/

  Charcot-Marie-Tooth disease can be caused by mutations in many different genes. These genes provide instructions for making proteins that are involved in the function of peripheral nerves in the feet, legs, and hands. The gene mutations that cause Charcot-Marie-Tooth disease affect the function of the proteins in ways that are not fully understood; however, they likely impair axons, which transmit nerve impulses, or affect the specialized cells that produce myelin. In most cases, longer nerves that transmit impulses to the appendages of the body are more likely to be affected. As a result, peripheral nerve cells slowly lose the ability to stimulate the muscles in the feet, legs, and eventually the hands, and to transmit sensory signals from these appendages to the brain. Different mutations within a single gene may cause signs and symptoms of differing severities or lead to different types of Charcot-Marie-Tooth disease.

• #8 Charcot-Marie-Tooth disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/charcot-marie-tooth-disease/

  Between 70 and 80 percent of individuals with CMT1 have mutations affecting the PMP22 gene. Most of these cases occur when there is an extra copy of the gene resulting from a small duplication of genetic material on chromosome 17. Another 10 to 12 percent of individuals with CMT1 have mutations in the MPZ gene. MPZ gene mutations are also occasionally identified in people with other forms of the disorder. The most common cause of CMT2 is mutations in the MFN2 gene, which accounts for about 20 percent of cases. Approximately 90 percent of people with CMTX have GJB1 gene mutations. Mutations in dozens of other genes have been identified in smaller numbers of people with these and the other types. The list of genes associated with Charcot-Marie-Tooth disease continues to grow as researchers study this disorder.

• #9 Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes

  https://www.pfmjournal.org/journal/view.php?doi=10.23838/pfm.2018.00163

  Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neuropathies and is both genetically and clinically heterogeneous, with variable inheritance modes. […] Up to date, more than 90 causative genes for CMT have been identified. […] Therefore, accurate genetic diagnosis is of crucial importance when performing customized therapy. […] Recent investigations on induced pluripotent stem cells expanded the possibility of both patient-specific cell therapy and drug discovery. […] As more than 90 causative genes for CMT were found up to date, this disease is categorized into numerous subtypes. […] Recent studies reported a dominant inheritance of PMP2 mutations in demyelinating CMT patients. […] CMT2 was reported to occur less frequently than CMT1 and to represent about one-third of the total CMT cases.

• #10 Charcot-Marie-Tooth Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562163/

  CMT and related disorders are genetically determined, involving more than 100 genes. About 80% to 90% of the genetic abnormalities are due to copy number variations (CNVs) in peripheral myelin protein 22 (PMP22) and mutations in GJB1, MPZ, and MFN2 genes. Only a few families are affected by mutations in other genes, and 18% to 50% of cases remain unsolved, possibly due to mutations in noncoding DNA or structural variations. Structural variations describe genomic rearrangements that disrupt chromosomal organization and architecture, including duplications and deletions (also referred to as CNV), insertions, inversions, and translocations. […] Autosomal dominant CMT is the most common genetic subtype, followed by X-linked CMT, while autosomal recessive forms are rare. […] About 90% of mutations in individuals with CMT type 1 are caused by 3 genetic defects PMP22 duplication, GJB1 point mutations, and MPZ point mutations which cause damage to Schwann cells and the myelin sheath of the axon. CMT type 1A, the most common CMT neuropathy, is caused by a 1.5-Mb duplication of chromosome 17p11.2, resulting in trisomy of PMP22. Due to its large size, this region is susceptible to frequent genomic rearrangements. Duplication or deletion in PMP22 leads to disease via a gene dosage effect, given the sensitivity of nervous tissue to the gain or loss of a copy of the PMP22 gene.

• #11 Charcot–Marie–Tooth disease – Wikipedia

  https://en.wikipedia.org/wiki/Charcot%E2%80%93Marie%E2%80%93Tooth_disease

  Charcot-Marie-Tooth (CMT) disease is an inherited neurological disorder primarily caused by genetic mutations that disrupt critical proteins within peripheral nerves. […] These mutations predominantly affect proteins essential for the structure and function of the myelin sheath, including peripheral myelin protein 22 (PMP22), myelin protein zero (P0/MPZ), connexin32 (Cx32/GJB1), and periaxin (PRX), leading to demyelination. […] Additionally, mutations in proteins involved in axonal integrity, such as neurofilament light chain (NF-L), dynamin 2 (DNM2), ganglioside-induced differentiation-associated protein 1 (GDAP1), and mitofusin 2 (MFN2), can cause axonal forms of CMT. […] The most common cause (70-80% of cases) of CMT is a duplication on the short arm of chromosome 17, involving the gene PMP22. […] In some forms like X-linked CMT (CMTX), mutations in the GJB1 gene lead to dysfunction in gap junctions within Schwann cells, further impairing nerve signal transmission.

• #12 Charcot-Marie-Tooth disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/charcot-marie-tooth-disease/

  Between 70 and 80 percent of individuals with CMT1 have mutations affecting the PMP22 gene. Most of these cases occur when there is an extra copy of the gene resulting from a small duplication of genetic material on chromosome 17. Another 10 to 12 percent of individuals with CMT1 have mutations in the MPZ gene. MPZ gene mutations are also occasionally identified in people with other forms of the disorder. The most common cause of CMT2 is mutations in the MFN2 gene, which accounts for about 20 percent of cases. Approximately 90 percent of people with CMTX have GJB1 gene mutations. Mutations in dozens of other genes have been identified in smaller numbers of people with these and the other types. The list of genes associated with Charcot-Marie-Tooth disease continues to grow as researchers study this disorder.

• #13 Charcot-Marie-Tooth disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/charcot-marie-tooth-disease/

  Between 70 and 80 percent of individuals with CMT1 have mutations affecting the PMP22 gene. Most of these cases occur when there is an extra copy of the gene resulting from a small duplication of genetic material on chromosome 17. Another 10 to 12 percent of individuals with CMT1 have mutations in the MPZ gene. MPZ gene mutations are also occasionally identified in people with other forms of the disorder. The most common cause of CMT2 is mutations in the MFN2 gene, which accounts for about 20 percent of cases. Approximately 90 percent of people with CMTX have GJB1 gene mutations. Mutations in dozens of other genes have been identified in smaller numbers of people with these and the other types. The list of genes associated with Charcot-Marie-Tooth disease continues to grow as researchers study this disorder.

• #14 Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes

  https://www.pfmjournal.org/journal/view.php?doi=10.23838/pfm.2018.00163

  Several genes associated with CMT2 were identified and studies were conducted to identify its mutation frequencies and specific clinical types. […] Mutations in the mitofusin 2 (MFN2) gene, which plays an important role in mitochondrial function, account for more than 33% of the CMT2 subtype. […] CMT3 is caused by mutations in the following genes; the MPZ, PMP22, periaxin (PRX), and EGR2 genes. […] CMT4 belongs to the genetically heterogeneous group of CMT peripheral sensorimotor polyneuropathies. […] Autosomal recessive demyelinating CMT disease type 4A is caused by a mutation in the gene encoding GDAP1 on chromosome 8q21. […] CMT5 was originally described in patients with peroneal muscular atrophy and hereditary spastic paraparesis. […] CMT6 is caused by a heterozygous mutation in the MFN2 gene on chromosome 1p36.

• #15 Charcot-Marie-Tooth disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/charcot-marie-tooth-disease/

  Between 70 and 80 percent of individuals with CMT1 have mutations affecting the PMP22 gene. Most of these cases occur when there is an extra copy of the gene resulting from a small duplication of genetic material on chromosome 17. Another 10 to 12 percent of individuals with CMT1 have mutations in the MPZ gene. MPZ gene mutations are also occasionally identified in people with other forms of the disorder. The most common cause of CMT2 is mutations in the MFN2 gene, which accounts for about 20 percent of cases. Approximately 90 percent of people with CMTX have GJB1 gene mutations. Mutations in dozens of other genes have been identified in smaller numbers of people with these and the other types. The list of genes associated with Charcot-Marie-Tooth disease continues to grow as researchers study this disorder.

• #16 Charcot-Marie-Tooth Disease – CMT is the Biggest Disease No one Has heard of, Until Now

  https://www.hnf-cure.org/cmt/what-is-cmt/

  Charcot-Marie-Tooth disease (CMT), named after the three doctors who first identified it, is one of the most common inherited nerve disorders and is also referred to as hereditary sensory and motor neuropathy (HSMN). […] There are over 100 different genes that cause CMT. Approximately 95% are diagnosed with the 4 most prevalent types of CMT: PMP22, MPZ, MFN2 and GJB1. […] Mutations in four genes (PMP22 dup/del, GJB1, MPZ, and MFN2) accounted for 94.9% of the genetically positive patients in our cohort. PMP22 duplications (dup) accounted 56.7% of positive patients, PMP22 deletions (del) 21.9%, GJB1 6.7%, MPZ 5.3%, MFN2 4.3%.

• #17 Charcot-Marie-Tooth (CMT) Disease – Kane Hall Barry Neurology

  https://kanehallbarry.com/conditions/charcot-marie-tooth-cmt-disease/

  Charcot-Marie-Tooth disease (CMT) affects 1 in 2,500 people and is caused by mutations in more than 30 genes. […] About 90% of individuals with CMT inherit it from a parent, with the remaining 10% resulting from spontaneous genetic mutations. Though there are a myriad of gene associations and mechanisms, four genes comprise over 90% of genetically confirmed cases of CMT.

• #18 Analyzing clinical and genetic aspects of axonal Charcot–Marie-Tooth disease

  https://www.e-kjgm.org/journal/view.html?doi=10.5734/JGM.2021.18.2.83

  CharcotMarie-Tooth disease (CMT) is the most common hereditary motor and sensory peripheral neuropathy. […] To date, more than 130 causative genes for CMT have been reported. […] Until now, the causative gene mutation underlying CMT could be identified in only 60% to 70% of all CMT patients, while that in the others could not be identified even by using WES. Therefore, the WGS test is needed to investigate the causative genes of those that are remaining. The cause of CMT may be a regulatory gene in the intron, a splicing mutation, copy number variation, structural variation, or transposal element. […] Accurate diagnosis based on genotype/phenotype correlation is essential in CMT2, and PGD is, therefore, widely used in CMT2 patients.

• #19 Charcot–Marie–Tooth disease | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg200931

  Some of these genes/mutations contribute to a significant fraction of inherited peripheral neuropathy cases and thus molecular analysis can have a substantial function in establishing a precise molecular diagnosis. […] Genetic heterogeneity, age-dependent penetrance and variable expressivity are key characteristics of CMT and related peripheral neuropathies. […] Thirty-six loci and more than two dozen genes are involved in CMT, implicating pathways in myelination, radial and axonal transport, Schwann cell differentiation, signal transduction, mitochondrial function, endosome, protein translation and single-stranded DNA break repair. […] Genotype-phenotype correlation studies suggest that genetic heterogeneity, age-dependent penetrance and variable expressivity significantly contribute to the genetics of CMT.

• #20 Charcot-Marie-Tooth Disease (CMT): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/6009-charcot-marie-tooth-disease-cmt

  CMT type 1 (CMT1): This type affects myelin, causing slowed signals. It usually appears between ages 10 and 40, but some people can live for decades without developing any symptoms. This is the most common type of CMT, happening about twice as often as CMT2. CMT2: This type involves axon problems. Nerve signals are weaker and may travel slightly slower, too. It accounts for about one-third of CMT cases.

• #21 Charcot-Marie-Tooth Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562163/

  CMT and related disorders are genetically determined, involving more than 100 genes. About 80% to 90% of the genetic abnormalities are due to copy number variations (CNVs) in peripheral myelin protein 22 (PMP22) and mutations in GJB1, MPZ, and MFN2 genes. Only a few families are affected by mutations in other genes, and 18% to 50% of cases remain unsolved, possibly due to mutations in noncoding DNA or structural variations. Structural variations describe genomic rearrangements that disrupt chromosomal organization and architecture, including duplications and deletions (also referred to as CNV), insertions, inversions, and translocations. […] Autosomal dominant CMT is the most common genetic subtype, followed by X-linked CMT, while autosomal recessive forms are rare. […] About 90% of mutations in individuals with CMT type 1 are caused by 3 genetic defects PMP22 duplication, GJB1 point mutations, and MPZ point mutations which cause damage to Schwann cells and the myelin sheath of the axon. CMT type 1A, the most common CMT neuropathy, is caused by a 1.5-Mb duplication of chromosome 17p11.2, resulting in trisomy of PMP22. Due to its large size, this region is susceptible to frequent genomic rearrangements. Duplication or deletion in PMP22 leads to disease via a gene dosage effect, given the sensitivity of nervous tissue to the gain or loss of a copy of the PMP22 gene.

• #22 Charcot-Marie-Tooth Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562163/

  Duplication in the heterozygous state results in 1.5-fold overexpression of PMP22 in Schwann cells, while homozygous duplication causes 2-fold overexpression. This genomic duplication results from an unequal meiotic crossover facilitated in the male germline by flanking homologous repeat sequences. In laboratory models, this overexpression overloads the proteasome system, leading to cytoplasmic aggregation of the ubiquitinated PMP22 protein, recruitment of autophagosomes and lysosomes, and increased autophagy. […] Frameshift mutations in MPZ lead to mutant proteins aggregating in the endoplasmic reticulum of the neuron and consequent apoptosis. Other variations of CMT are usually the result of loss-of-function mutations in different genes and are uncommonly due to a toxic gain of function.

• #23 Charcot-Marie-Tooth Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562163/

  Duplication in the heterozygous state results in 1.5-fold overexpression of PMP22 in Schwann cells, while homozygous duplication causes 2-fold overexpression. This genomic duplication results from an unequal meiotic crossover facilitated in the male germline by flanking homologous repeat sequences. In laboratory models, this overexpression overloads the proteasome system, leading to cytoplasmic aggregation of the ubiquitinated PMP22 protein, recruitment of autophagosomes and lysosomes, and increased autophagy. […] Frameshift mutations in MPZ lead to mutant proteins aggregating in the endoplasmic reticulum of the neuron and consequent apoptosis. Other variations of CMT are usually the result of loss-of-function mutations in different genes and are uncommonly due to a toxic gain of function.

• #24 Charcot-Marie-Tooth Disease (CMT): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/6009-charcot-marie-tooth-disease-cmt

  CMT type 1 (CMT1): This type affects myelin, causing slowed signals. It usually appears between ages 10 and 40, but some people can live for decades without developing any symptoms. This is the most common type of CMT, happening about twice as often as CMT2. CMT2: This type involves axon problems. Nerve signals are weaker and may travel slightly slower, too. It accounts for about one-third of CMT cases.

• #25 Charcot-Marie-Tooth disease – CheckOrphan

  https://checkorphan.org/disease/charcot-marie-tooth-disease/

  CharcotMarieTooth disease is caused by mutations that cause defects in neuronal proteins. Nerve signals are conducted by an axon with a myelin sheath wrapped around it. Most mutations in CMT affect the myelin sheath, but some affect the axon. […] The most common cause of CMT (70-80% of the cases) is the duplication of a large region on the short arm of chromosome 17 that includes the gene PMP22. Some mutations affect the gene MFN2, which codes for a mitochondrial protein. […] In some forms of CMT, mutated MFN2 causes the mitochondria to form large clusters, or clots, which are unable to travel down the axon towards the synapses. This prevents the synapses from functioning. […] CMT is divided into the primary demyelinating neuropathies (CMT1, CMT3, and CMT4) and the primary axonal neuropathies (CMT2), with frequent overlap. […] Demyelinating Schwann cells causes abnormal axon structure and function. They may cause axon degeneration, or they may simply cause axons to malfunction.

• #26 Charcot–Marie–Tooth disease – Wikipedia

  https://en.wikipedia.org/wiki/Charcot%E2%80%93Marie%E2%80%93Tooth_disease

  Charcot-Marie-Tooth (CMT) disease is an inherited neurological disorder primarily caused by genetic mutations that disrupt critical proteins within peripheral nerves. […] These mutations predominantly affect proteins essential for the structure and function of the myelin sheath, including peripheral myelin protein 22 (PMP22), myelin protein zero (P0/MPZ), connexin32 (Cx32/GJB1), and periaxin (PRX), leading to demyelination. […] Additionally, mutations in proteins involved in axonal integrity, such as neurofilament light chain (NF-L), dynamin 2 (DNM2), ganglioside-induced differentiation-associated protein 1 (GDAP1), and mitofusin 2 (MFN2), can cause axonal forms of CMT. […] The most common cause (70-80% of cases) of CMT is a duplication on the short arm of chromosome 17, involving the gene PMP22. […] In some forms like X-linked CMT (CMTX), mutations in the GJB1 gene lead to dysfunction in gap junctions within Schwann cells, further impairing nerve signal transmission.

• #27 Charcot-Marie-Tooth Disease | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/charcot-marie-tooth-disease

  Charcot-Marie-Tooth disease (CMT) is a group of genetic conditions that affect the nerves connecting the brain and spinal cord to the rest of the body. […] More than 100 genes are linked to CMT. Depending on the gene problem, CMT can affect the axon, the myelin sheath, or both. […] Although different forms of CMT involve mutations in different genes that produce proteins needed for the axon or myelin to work, all forms of CMT affect the function of peripheral nerves. Gene defects in myelin and the axons can cause them to stop working as they should, disrupting nerve signals and sometimes leading to nerve loss. […] CMT is mostly an inherited disorder, and people with a family history of Charcot-Marie-Tooth (CMT) disease are more likely to develop it. […] People inherit CMT gene mutations in three main ways: autosomal dominant, autosomal recessive, and X-linked.

• #28 Understanding CMT: Symptoms & Management

  https://www.cmtausa.org/understanding-cmt/what-is-cmt/

  Named after the three doctors who first described it in 1886: Charcot (shar-coh), Marie, and Tooth, Charcot-Marie-Tooth disease (CMT) is an inheritable peripheral neuropathy that includes many motor and/or sensory neuropathies, axonopathies, myelinopathies, and neuronopathies. […] CMT AFFECTS ONE IN EVERY 2,500 PEOPLE a rare disease subdivided into multiple subtypes, each with a lower prevalence. Although CMT is a rare disease, it is also the most common inherited peripheral neuropathy. […] CMTA HAS CATALOGED MORE THAN 160 INDIVIDUAL TYPES OF CMT, each caused by one of many various mutations in more than 130 genes CMTA has also cataloged. […] CMT IS INHERITED IN ONE OF FIVE DIFFERENT WAYS, and each is an inheritance pattern. CMTs five inheritance patterns are autosomal dominant, autosomal recessive, X-Linked dominant, X-Linked recessive, and one type is inherited via mitochondrial inheritance.

• #29 Charcot-Marie-Tooth Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562163/

  CMT and related disorders are genetically determined, involving more than 100 genes. About 80% to 90% of the genetic abnormalities are due to copy number variations (CNVs) in peripheral myelin protein 22 (PMP22) and mutations in GJB1, MPZ, and MFN2 genes. Only a few families are affected by mutations in other genes, and 18% to 50% of cases remain unsolved, possibly due to mutations in noncoding DNA or structural variations. Structural variations describe genomic rearrangements that disrupt chromosomal organization and architecture, including duplications and deletions (also referred to as CNV), insertions, inversions, and translocations. […] Autosomal dominant CMT is the most common genetic subtype, followed by X-linked CMT, while autosomal recessive forms are rare. […] About 90% of mutations in individuals with CMT type 1 are caused by 3 genetic defects PMP22 duplication, GJB1 point mutations, and MPZ point mutations which cause damage to Schwann cells and the myelin sheath of the axon. CMT type 1A, the most common CMT neuropathy, is caused by a 1.5-Mb duplication of chromosome 17p11.2, resulting in trisomy of PMP22. Due to its large size, this region is susceptible to frequent genomic rearrangements. Duplication or deletion in PMP22 leads to disease via a gene dosage effect, given the sensitivity of nervous tissue to the gain or loss of a copy of the PMP22 gene.

• #30 Charcot-Marie-Tooth disease (CMT) – Muscular Dystrophy UK

  https://www.musculardystrophyuk.org/conditions/a-z/charcot-marie-tooth-disease-cmt/

  Charcot-Marie-Tooth disease (CMT) is caused by changes in genes that affect the peripheral nerves. These nerves connect the brain and spinal cord to the rest of the body. They carry messages and control movement. Peripheral nerves can be thought of like an electrical copper wire. They have a core, called an axon, that connects the spinal cord to the arms and legs. There is insulation around the core, called the myelin sheath, which is like the plastic insulation around electrical wires. In CMT type 1, genes damage the myelin sheath, and in CMT type 2, they damage the axon. When the specific genetic change is known, CMT is further grouped into subtypes. For example, the most common subtype is CMT1A and is linked to a change in the PMP22 gene. […] Most subtypes of CMT type 1 and type 2 are inherited in an autosomal dominant pattern. This means that a person only needs to inherit the genetic change from one parent to have the condition.

• #31 Charcot-Marie-Tooth disease – myDr.com.au

  https://mydr.com.au/first-aid-self-care/charcot-marie-tooth-disease/

  CMT1A is the most common form of CMT accounting for at least 60 percent of all patients with CMT Type 1. It is caused by the presence of an extra copy of a gene that carries the information for making a protein called peripheral myelin protein 22 (PMP22). In these patients excessive amounts of PMP22 are produced which impairs the formation of the myelin sheath. […] More rarely, CMT is inherited in an autosomal recessive pattern which means that for an individual to develop the condition they need to inherit two altered genes one from each parent. The parents of an individual with this type of CMT each carry one copy of the altered gene, and are known as carriers, but they typically do not have symptoms of the condition. […] Understandably, the greatest is known about the most common type of CMT CMT1A which is caused by the presence of an extra copy of a gene that carries the information for making a protein called peripheral myelin protein 22 (PMP22). This results in excessive amounts of PMP22 being produced which impairs the formation of the myelin sheath. Treatment strategies currently being developed for CMT1A involve reducing the production of PMP22 protein.

• #32 Charcot-Marie-Tooth disease and hereditary motor neuropathies – Update 2020

  https://www.degruyter.com/document/doi/10.1515/medgen-2020-2038/html?lang=en

  CMT results from dysfunction of lower motor neurons and sensory neurons in dorsal root ganglia or their ensheathing glial cells (Schwann cells). […] CMT, dHMN, and HSAN are genetically highly heterogeneous with close to 100 different genes involved while there is one single major gene for HNPP. […] Three genetic defects (PMP22 duplication, GJB1 or MPZ point mutations) are responsible for about 90% of detectable mutations in patients with demyelinating CMT1. […] Similarly, the contribution of the three main genetic defects in axonal CMT2 (GJB1, MFN2, and MPZ mutations) to all CMT2 cases with a genetic diagnosis is about 80-85%. […] In patients with autosomal recessive inheritance, the clinical picture is often more severe and starts in early childhood or even infancy. […] Demyelinating autosomal recessive CMT is classified in OMIM as CMT4 and axonal autosomal recessive CMT as axonal AR-CMT.

• #33 Charcot-Marie-Tooth disease (CMT) – Muscular Dystrophy UK

  https://www.musculardystrophyuk.org/conditions/a-z/charcot-marie-tooth-disease-cmt/

  An exception is CMTX, which is inherited through the X chromosome. This pattern of inheritance is called X-linked recessive. As males have only one X chromosome, and females have two, males tend to be more affected by CMTX. This also means that males can’t pass on CMTX to their male children, but affected females, even mildly, can pass it on to their male children who are likely to have more severe symptoms.

• #34 Understanding CMT: Symptoms & Management

  https://www.cmtausa.org/understanding-cmt/what-is-cmt/

  Named after the three doctors who first described it in 1886: Charcot (shar-coh), Marie, and Tooth, Charcot-Marie-Tooth disease (CMT) is an inheritable peripheral neuropathy that includes many motor and/or sensory neuropathies, axonopathies, myelinopathies, and neuronopathies. […] CMT AFFECTS ONE IN EVERY 2,500 PEOPLE a rare disease subdivided into multiple subtypes, each with a lower prevalence. Although CMT is a rare disease, it is also the most common inherited peripheral neuropathy. […] CMTA HAS CATALOGED MORE THAN 160 INDIVIDUAL TYPES OF CMT, each caused by one of many various mutations in more than 130 genes CMTA has also cataloged. […] CMT IS INHERITED IN ONE OF FIVE DIFFERENT WAYS, and each is an inheritance pattern. CMTs five inheritance patterns are autosomal dominant, autosomal recessive, X-Linked dominant, X-Linked recessive, and one type is inherited via mitochondrial inheritance.

• #35 Charcot-Marie-Tooth Disease (CMT): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/6009-charcot-marie-tooth-disease-cmt

  Charcot-Marie-Tooth disease (CMT) is a condition that affects the nerves that control muscle movements. There are six main types of CMT, all of which happen because of a genetic mutation you inherited from one or both parents. […] CMT can involve mutations in one gene or several. So far, researchers have identified several dozen different gene mutations that can cause the different forms of CMT. […] You can have a DNA mutation in one of two ways: Inherited: These DNA mutations pass to you from one or both parents. Spontaneous: You develop these mutations while you’re still an embryo developing in the uterus. They’re sometimes called de novo mutations, which means new. […] Yes, there are seven main types of Charcot-Marie-Tooth disease, but CMT types 1 and 2 are the most common. The other forms are very or extremely rare.

• #36 Charcot-Marie-Tooth (CMT) Disease – Kane Hall Barry Neurology

  https://kanehallbarry.com/conditions/charcot-marie-tooth-cmt-disease/

  Charcot-Marie-Tooth (CMT) disease is a hereditary neurological disorder that affects the peripheral nerves, responsible for transmitting signals between the brain, spinal cord, and muscles. CMT, also known as hereditary motor and sensory neuropathy, is one of the most common inherited neurological disorders, affecting an estimated 126,000 individuals in the United States and 2.6 million people worldwide. The disease is progressive, leading to muscle weakness and atrophy, particularly in the feet, legs, hands, and arms, and can significantly impact a person’s quality of life. […] CMT is caused by genetic mutations that affect the structure and function of peripheral nerves. The disease is primarily inherited in an autosomal dominant manner, meaning only one copy of the mutated gene from one parent is required to develop the disease. About 90% of people with CMT inherit it from a parent with the condition, while the remaining cases are due to spontaneous mutations.

• #37 Charcot-Marie-Tooth Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1232386-overview

  HMSNs are classified by Online Mendelian Inheritance in Man (OMIM). A broad division may be made between HMSNs with diffusely slow nerve conduction velocity and those with normal or borderline abnormal nerve conduction velocity. […] HMSN I (ie, CMT 1) includes the following subtypes: CMT 1A – Autosomal dominant band 17p11.2-12 is most common; milder than CMT 1B, CMT 1B – Autosomal dominant band 1q21-25, CMT 1C – Unknown autosome, CMT X1 – X-linked dominant band Xq13-21, CMT X2 and CMT X3 – X-linked recessive, Autosomal recessive CMT 1 – Arm 8q. […] HMSN III (Dejerine-Sottas disease, hypertrophic neuropathy of infancy, congenital hypomyelinated neuropathy) is inherited in an autosomal recessive manner. […] HMSN IV (Refsum syndrome, phytanic acid excess) has an autosomal recessive inheritance and is characterized by a tetrad of peripheral neuropathy, retinitis pigmentosa, cerebellar signs, and increased cerebrospinal fluid (CSF) protein.

• #38 Charcot-Marie-Tooth disease and hereditary motor neuropathies – Update 2020

  https://www.degruyter.com/document/doi/10.1515/medgen-2020-2038/html?lang=en

  Inherited peripheral neuropathy is the most common hereditary neuromuscular disease with a prevalence of about 1:2,500. […] With the exception of HNPP, which is almost always caused by defects of the PMP22 gene, all other forms show genetic heterogeneity with altogether more than 100 genes involved. […] Based on current information, analysis of only four genes (PMP22, GJB1, MPZ, MFN2) identifies 80-90% of CMT-causing mutations that can be detected in all known disease genes. […] Charcot-Marie-Tooth (CMT) disease, also denoted as hereditary motor and sensory neuropathy (HMSN), is clinically and genetically closely related to hereditary neuropathy with liability to pressure palsies (HNPP) and distal hereditary motor neuropathies (dHMN), also known as distal spinal muscular atrophy (DSMA).

• #39 Charcot-Marie-Tooth Disease (CMT): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/6009-charcot-marie-tooth-disease-cmt

  CMT type 1 (CMT1): This type affects myelin, causing slowed signals. It usually appears between ages 10 and 40, but some people can live for decades without developing any symptoms. This is the most common type of CMT, happening about twice as often as CMT2. CMT2: This type involves axon problems. Nerve signals are weaker and may travel slightly slower, too. It accounts for about one-third of CMT cases.

• #40 Charcot-Marie-Tooth Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1232386-overview

  HMSNs are classified by Online Mendelian Inheritance in Man (OMIM). A broad division may be made between HMSNs with diffusely slow nerve conduction velocity and those with normal or borderline abnormal nerve conduction velocity. […] HMSN I (ie, CMT 1) includes the following subtypes: CMT 1A – Autosomal dominant band 17p11.2-12 is most common; milder than CMT 1B, CMT 1B – Autosomal dominant band 1q21-25, CMT 1C – Unknown autosome, CMT X1 – X-linked dominant band Xq13-21, CMT X2 and CMT X3 – X-linked recessive, Autosomal recessive CMT 1 – Arm 8q. […] HMSN III (Dejerine-Sottas disease, hypertrophic neuropathy of infancy, congenital hypomyelinated neuropathy) is inherited in an autosomal recessive manner. […] HMSN IV (Refsum syndrome, phytanic acid excess) has an autosomal recessive inheritance and is characterized by a tetrad of peripheral neuropathy, retinitis pigmentosa, cerebellar signs, and increased cerebrospinal fluid (CSF) protein.

• #41 Charcot-Marie-Tooth disease – myDr.com.au

  https://mydr.com.au/first-aid-self-care/charcot-marie-tooth-disease/

  CMT1A is the most common form of CMT accounting for at least 60 percent of all patients with CMT Type 1. It is caused by the presence of an extra copy of a gene that carries the information for making a protein called peripheral myelin protein 22 (PMP22). In these patients excessive amounts of PMP22 are produced which impairs the formation of the myelin sheath. […] More rarely, CMT is inherited in an autosomal recessive pattern which means that for an individual to develop the condition they need to inherit two altered genes one from each parent. The parents of an individual with this type of CMT each carry one copy of the altered gene, and are known as carriers, but they typically do not have symptoms of the condition. […] Understandably, the greatest is known about the most common type of CMT CMT1A which is caused by the presence of an extra copy of a gene that carries the information for making a protein called peripheral myelin protein 22 (PMP22). This results in excessive amounts of PMP22 being produced which impairs the formation of the myelin sheath. Treatment strategies currently being developed for CMT1A involve reducing the production of PMP22 protein.

• #42 Charcot-Marie-Tooth Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1232386-overview

  HMSNs are classified by Online Mendelian Inheritance in Man (OMIM). A broad division may be made between HMSNs with diffusely slow nerve conduction velocity and those with normal or borderline abnormal nerve conduction velocity. […] HMSN I (ie, CMT 1) includes the following subtypes: CMT 1A – Autosomal dominant band 17p11.2-12 is most common; milder than CMT 1B, CMT 1B – Autosomal dominant band 1q21-25, CMT 1C – Unknown autosome, CMT X1 – X-linked dominant band Xq13-21, CMT X2 and CMT X3 – X-linked recessive, Autosomal recessive CMT 1 – Arm 8q. […] HMSN III (Dejerine-Sottas disease, hypertrophic neuropathy of infancy, congenital hypomyelinated neuropathy) is inherited in an autosomal recessive manner. […] HMSN IV (Refsum syndrome, phytanic acid excess) has an autosomal recessive inheritance and is characterized by a tetrad of peripheral neuropathy, retinitis pigmentosa, cerebellar signs, and increased cerebrospinal fluid (CSF) protein.

• #43 Charcot-Marie-Tooth disease (CMT) | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/charcot-marie-tooth-disease-cmt

  Charcot-Marie-Tooth disease (CMT) is an umbrella term for a range of certain inherited genetic conditions that affect the peripheral nervous system. […] CMT either interferes with the production of proteins that make up the myelin sheath, or else affects the structure or function of the axon. […] CMT is the most common inherited condition affecting the peripheral nervous system. […] Most inherited conditions can only be passed on by one or two patterns of inheritance. However, CMT can be inherited via most known patterns of inheritance and is the most common inherited condition of the peripheral nervous system. Patterns of inheritance for CMT include: autosomal dominant, autosomal recessive, and X-linked. […] The causes of the various types of CMT include: CMT Type 1A a duplicated gene on chromosome 17, CMT Type 1B a genetic change on chromosome 1, CMT Type 1C a genetic change on chromosome 16, CMT Type X-linked a genetic change on the X chromosome, CMT Type 2A a genetic change on chromosome 1, CMT Type 2B a genetic change on chromosome 3, CMT Type 2C a genetic change on chromosome 12, CMT Type 2D a genetic change on chromosome 7. […] Recently, a number of new genes have been discovered, which cause some less common forms of CMT.

• #44 Azthena logo with the word Azthena

  https://www.news-medical.net/health/CharcotMarieTooth-Disease-(CMT).aspx

  CharcotMarieTooth disease (CMT) results due to certain gene alterations and is also named as hereditary motor and sensory neuropathy (HMSN) or peroneal muscular atrophy. […] CMT occurs either due to the defect in the nerve axon or due to the damage to the myelin sheath layering the axons, thereby resulting in cessation of the electrical signals transmitted by the nerves. […] CharcotMarieTooth disease can be inherited in an autosomal recessive, autosomal dominant, or X-linked dominant fashion. […] Mutation of PMP-22, P0, LITAF, EDFR, or NEFL genes can result in CMT, which leads to the destruction of the myelin sheath. […] Injury to the axons can result from the mutation in the mitofusin-2, RAB7, GARS, NEFL, HSP27, or HSP22 gene. […] Alterations in the P0 or PMP-22 gene results in an acute and rapid onset of the symptoms; these sets of mutations are categorized under CMT3. […] CMT4 results from the mutations of GDAP1, MEMR13, MYMR2, SH3TC2, NDG1, EGR2, PRX, FDG4, or FIG4 gene, whereas alterations in the X chromosome results in CMTX.

• #45 A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy | PLOS Genetics

  https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005829

  Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of peripheral neuropathies with diverse genetic causes. […] The most frequent genetic cause of CMT1 is alterations in PMP22, resulting in CMT1A or CMT1E, followed by MPZ mutations, which lead to CMT1B. […] Intriguingly, mutations in Myelin basic protein (MBP) and Peripheral myelin protein 2 (PMP2), which account for 18% and 5% of peripheral myelin proteins, have not been reported as a genetic cause of CMT. […] Recently, a point mutation (p.I43N) in PMP2 was strongly suggested as a potential pathogenic mutation in a family with autosomal dominant CMT1. […] This study strongly suggests that PMP2 mutation is the underlying cause of an autosomal dominant CMT1 phenotype. […] The same mutation in PMP2 was also suggested as a strong candidate for the cause of another CMT1 family.

• #46 Charcot-Marie-Tooth Disease (CMT): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/6009-charcot-marie-tooth-disease-cmt

  CMT type 1 (CMT1): This type affects myelin, causing slowed signals. It usually appears between ages 10 and 40, but some people can live for decades without developing any symptoms. This is the most common type of CMT, happening about twice as often as CMT2. CMT2: This type involves axon problems. Nerve signals are weaker and may travel slightly slower, too. It accounts for about one-third of CMT cases.

• #47 Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes

  https://www.pfmjournal.org/journal/view.php?doi=10.23838/pfm.2018.00163

  Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neuropathies and is both genetically and clinically heterogeneous, with variable inheritance modes. […] Up to date, more than 90 causative genes for CMT have been identified. […] Therefore, accurate genetic diagnosis is of crucial importance when performing customized therapy. […] Recent investigations on induced pluripotent stem cells expanded the possibility of both patient-specific cell therapy and drug discovery. […] As more than 90 causative genes for CMT were found up to date, this disease is categorized into numerous subtypes. […] Recent studies reported a dominant inheritance of PMP2 mutations in demyelinating CMT patients. […] CMT2 was reported to occur less frequently than CMT1 and to represent about one-third of the total CMT cases.

• #48 Charcot-Marie-Tooth Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1232386-overview

  HMSN II (ie, CMT 2) includes the following subtypes: CMT 2A – Band 1p35-36; typical type; no enlarged nerves; later onset of symptoms; feet are more severely affected than hands, CMT 2B – Band 3q13-22; typical type with axonal spheroids, CMT 2C – Not linked to any known loci; diaphragm and vocal cord weakness, CMT 2D – Band 7p14; muscle weakness and atrophy more severe in hands than in feet, Autosomal recessive CMT 2. […] Genetic and clinical features of CMT disorders are listed in Table 1 below.

• #49 CMT Disease Type 2A: What Is It? | CMT Research Foundation

  https://cmtrf.org/what-is-cmt-disease/types-of-cmt/cmt2/what-is-cmt2a/

  Charcot-Marie-Tooth disease type 2A is a form of CMT inherited in an autosomal dominant manner. This means that you can inherit the disease from either parent if they also have the disease. However, it is important to remember that around 10% of CMT cases are “sporadic,” meaning that rather than being inherited from either of their parents, these individuals had the genetic mutation occur spontaneously during their embryonic development. […] CMT2A is caused by mutations in a gene called MFN2, which produces the protein mitofusin-2. […] The genetic cause of CMT2A is a disease-causing alteration, or mutation, in the gene MFN2. There are many known mutations in MFN2 that cause CMT2A. […] When the MFN2 gene is mutated, mitochondrial function is compromised and neurons in the peripheral nervous system become sick. Exactly how the mitochondria dysfunction and causes of disease symptoms are not fully understood yet. […] Most people with CMT also experience some loss of or changes in sensation, because the peripheral nerves carry sensory information in addition to movement signals.

• #50 Charcot-Marie-Tooth Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1232386-overview

  HMSN II (ie, CMT 2) includes the following subtypes: CMT 2A – Band 1p35-36; typical type; no enlarged nerves; later onset of symptoms; feet are more severely affected than hands, CMT 2B – Band 3q13-22; typical type with axonal spheroids, CMT 2C – Not linked to any known loci; diaphragm and vocal cord weakness, CMT 2D – Band 7p14; muscle weakness and atrophy more severe in hands than in feet, Autosomal recessive CMT 2. […] Genetic and clinical features of CMT disorders are listed in Table 1 below.

• #51 Charcot-Marie-Tooth Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1232386-overview

  HMSN II (ie, CMT 2) includes the following subtypes: CMT 2A – Band 1p35-36; typical type; no enlarged nerves; later onset of symptoms; feet are more severely affected than hands, CMT 2B – Band 3q13-22; typical type with axonal spheroids, CMT 2C – Not linked to any known loci; diaphragm and vocal cord weakness, CMT 2D – Band 7p14; muscle weakness and atrophy more severe in hands than in feet, Autosomal recessive CMT 2. […] Genetic and clinical features of CMT disorders are listed in Table 1 below.

• #52 Charcot-Marie-Tooth Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1232386-overview

  HMSN II (ie, CMT 2) includes the following subtypes: CMT 2A – Band 1p35-36; typical type; no enlarged nerves; later onset of symptoms; feet are more severely affected than hands, CMT 2B – Band 3q13-22; typical type with axonal spheroids, CMT 2C – Not linked to any known loci; diaphragm and vocal cord weakness, CMT 2D – Band 7p14; muscle weakness and atrophy more severe in hands than in feet, Autosomal recessive CMT 2. […] Genetic and clinical features of CMT disorders are listed in Table 1 below.

• #53 Charcot-Marie-Tooth disease (CMT) – Muscular Dystrophy UK

  https://www.musculardystrophyuk.org/conditions/a-z/charcot-marie-tooth-disease-cmt/

  An exception is CMTX, which is inherited through the X chromosome. This pattern of inheritance is called X-linked recessive. As males have only one X chromosome, and females have two, males tend to be more affected by CMTX. This also means that males can’t pass on CMTX to their male children, but affected females, even mildly, can pass it on to their male children who are likely to have more severe symptoms.

• #54 Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes

  https://www.pfmjournal.org/journal/view.php?doi=10.23838/pfm.2018.00163

  Several loci and genes are considered responsible for the following CMTX subtypes: Xq13 (GJB1; CMTX1), Xq26 (apoptosis-inducing factor mitochondria-associated 1 [AIFM1]; CMTX4), Xq22 (phosphoribosyl pyrophosphate synthetase 1 [PRPS1]; CMTX5), and Xp22 (pyruvate dehydrogenase kinase 3 [PDK3]; CMTX6). […] CMTX1 is caused by either hemizygous or heterozygous mutations in the GJB1 gene on chromosome Xq13. […] CMTX4 is caused by a mutation in the AIFM1 gene on chromosome Xq26. […] CMTX5 is caused by a LOF mutation in the PRPS1 gene on chromosome Xq22. […] CMTX6 is caused by a mutation in the PDK3 gene on chromosome Xp22.

• #55 Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes

  https://www.pfmjournal.org/journal/view.php?doi=10.23838/pfm.2018.00163

  Several loci and genes are considered responsible for the following CMTX subtypes: Xq13 (GJB1; CMTX1), Xq26 (apoptosis-inducing factor mitochondria-associated 1 [AIFM1]; CMTX4), Xq22 (phosphoribosyl pyrophosphate synthetase 1 [PRPS1]; CMTX5), and Xp22 (pyruvate dehydrogenase kinase 3 [PDK3]; CMTX6). […] CMTX1 is caused by either hemizygous or heterozygous mutations in the GJB1 gene on chromosome Xq13. […] CMTX4 is caused by a mutation in the AIFM1 gene on chromosome Xq26. […] CMTX5 is caused by a LOF mutation in the PRPS1 gene on chromosome Xq22. […] CMTX6 is caused by a mutation in the PDK3 gene on chromosome Xp22.

• #56 Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes

  https://www.pfmjournal.org/journal/view.php?doi=10.23838/pfm.2018.00163

  Several loci and genes are considered responsible for the following CMTX subtypes: Xq13 (GJB1; CMTX1), Xq26 (apoptosis-inducing factor mitochondria-associated 1 [AIFM1]; CMTX4), Xq22 (phosphoribosyl pyrophosphate synthetase 1 [PRPS1]; CMTX5), and Xp22 (pyruvate dehydrogenase kinase 3 [PDK3]; CMTX6). […] CMTX1 is caused by either hemizygous or heterozygous mutations in the GJB1 gene on chromosome Xq13. […] CMTX4 is caused by a mutation in the AIFM1 gene on chromosome Xq26. […] CMTX5 is caused by a LOF mutation in the PRPS1 gene on chromosome Xq22. […] CMTX6 is caused by a mutation in the PDK3 gene on chromosome Xp22.

• #57 Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes

  https://www.pfmjournal.org/journal/view.php?doi=10.23838/pfm.2018.00163

  Several loci and genes are considered responsible for the following CMTX subtypes: Xq13 (GJB1; CMTX1), Xq26 (apoptosis-inducing factor mitochondria-associated 1 [AIFM1]; CMTX4), Xq22 (phosphoribosyl pyrophosphate synthetase 1 [PRPS1]; CMTX5), and Xp22 (pyruvate dehydrogenase kinase 3 [PDK3]; CMTX6). […] CMTX1 is caused by either hemizygous or heterozygous mutations in the GJB1 gene on chromosome Xq13. […] CMTX4 is caused by a mutation in the AIFM1 gene on chromosome Xq26. […] CMTX5 is caused by a LOF mutation in the PRPS1 gene on chromosome Xq22. […] CMTX6 is caused by a mutation in the PDK3 gene on chromosome Xp22.

• #58 Charcot-Marie-Tooth Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1232386-overview

  HMSNs are classified by Online Mendelian Inheritance in Man (OMIM). A broad division may be made between HMSNs with diffusely slow nerve conduction velocity and those with normal or borderline abnormal nerve conduction velocity. […] HMSN I (ie, CMT 1) includes the following subtypes: CMT 1A – Autosomal dominant band 17p11.2-12 is most common; milder than CMT 1B, CMT 1B – Autosomal dominant band 1q21-25, CMT 1C – Unknown autosome, CMT X1 – X-linked dominant band Xq13-21, CMT X2 and CMT X3 – X-linked recessive, Autosomal recessive CMT 1 – Arm 8q. […] HMSN III (Dejerine-Sottas disease, hypertrophic neuropathy of infancy, congenital hypomyelinated neuropathy) is inherited in an autosomal recessive manner. […] HMSN IV (Refsum syndrome, phytanic acid excess) has an autosomal recessive inheritance and is characterized by a tetrad of peripheral neuropathy, retinitis pigmentosa, cerebellar signs, and increased cerebrospinal fluid (CSF) protein.

• #59 Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes

  https://www.pfmjournal.org/journal/view.php?doi=10.23838/pfm.2018.00163

  Several genes associated with CMT2 were identified and studies were conducted to identify its mutation frequencies and specific clinical types. […] Mutations in the mitofusin 2 (MFN2) gene, which plays an important role in mitochondrial function, account for more than 33% of the CMT2 subtype. […] CMT3 is caused by mutations in the following genes; the MPZ, PMP22, periaxin (PRX), and EGR2 genes. […] CMT4 belongs to the genetically heterogeneous group of CMT peripheral sensorimotor polyneuropathies. […] Autosomal recessive demyelinating CMT disease type 4A is caused by a mutation in the gene encoding GDAP1 on chromosome 8q21. […] CMT5 was originally described in patients with peroneal muscular atrophy and hereditary spastic paraparesis. […] CMT6 is caused by a heterozygous mutation in the MFN2 gene on chromosome 1p36.

• #60 Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes

  https://www.pfmjournal.org/journal/view.php?doi=10.23838/pfm.2018.00163

  Several genes associated with CMT2 were identified and studies were conducted to identify its mutation frequencies and specific clinical types. […] Mutations in the mitofusin 2 (MFN2) gene, which plays an important role in mitochondrial function, account for more than 33% of the CMT2 subtype. […] CMT3 is caused by mutations in the following genes; the MPZ, PMP22, periaxin (PRX), and EGR2 genes. […] CMT4 belongs to the genetically heterogeneous group of CMT peripheral sensorimotor polyneuropathies. […] Autosomal recessive demyelinating CMT disease type 4A is caused by a mutation in the gene encoding GDAP1 on chromosome 8q21. […] CMT5 was originally described in patients with peroneal muscular atrophy and hereditary spastic paraparesis. […] CMT6 is caused by a heterozygous mutation in the MFN2 gene on chromosome 1p36.

• #61 Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes

  https://www.pfmjournal.org/journal/view.php?doi=10.23838/pfm.2018.00163

  Several genes associated with CMT2 were identified and studies were conducted to identify its mutation frequencies and specific clinical types. […] Mutations in the mitofusin 2 (MFN2) gene, which plays an important role in mitochondrial function, account for more than 33% of the CMT2 subtype. […] CMT3 is caused by mutations in the following genes; the MPZ, PMP22, periaxin (PRX), and EGR2 genes. […] CMT4 belongs to the genetically heterogeneous group of CMT peripheral sensorimotor polyneuropathies. […] Autosomal recessive demyelinating CMT disease type 4A is caused by a mutation in the gene encoding GDAP1 on chromosome 8q21. […] CMT5 was originally described in patients with peroneal muscular atrophy and hereditary spastic paraparesis. […] CMT6 is caused by a heterozygous mutation in the MFN2 gene on chromosome 1p36.

• #62 MTMR2 Gene mutation causes rare Charcot-Marie-Tooth disease | TACG

  https://www.dovepress.com/identification-of-a-novel-homozygous-mutation-in-mtmr2-gene-causes-ver-peer-reviewed-fulltext-article-TACG

  CharcotMarieTooth disease (CMT) is a heterogeneous group of disorders involving peripheral nervous system. […] Germline mutations in MTMR2 gene causes CMT4B1. […] Mutations in myotubularin-related protein 2 (MTMR2), MTMR13 and MTMR5 causes CMT4B1, and CMT4B2 and CMT4B3, respectively. […] Germline mutations in MTMR2 cause CMT4B1. […] The present study reports the first mutation in the MTMR2 gene associated with CMT4B1 in a Chinese population. […] We identified a novel homozygous nonsense (c.118AT, p.Lys40*) mutation in MTMR2 in the proband. […] This mutation causes complete loss of all domains (the PH-GRAM Domain, Phosphatase Domain, Coiled-coil Domain and PDZ-Binding Motif) of the MTMR2 protein. […] The identified mutation resulted in the formation of a truncated MTMR2 protein with 39 amino acids.

• #63 MTMR2 Gene mutation causes rare Charcot-Marie-Tooth disease | TACG

  https://www.dovepress.com/identification-of-a-novel-homozygous-mutation-in-mtmr2-gene-causes-ver-peer-reviewed-fulltext-article-TACG

  CharcotMarieTooth disease (CMT) is a heterogeneous group of disorders involving peripheral nervous system. […] Germline mutations in MTMR2 gene causes CMT4B1. […] Mutations in myotubularin-related protein 2 (MTMR2), MTMR13 and MTMR5 causes CMT4B1, and CMT4B2 and CMT4B3, respectively. […] Germline mutations in MTMR2 cause CMT4B1. […] The present study reports the first mutation in the MTMR2 gene associated with CMT4B1 in a Chinese population. […] We identified a novel homozygous nonsense (c.118AT, p.Lys40*) mutation in MTMR2 in the proband. […] This mutation causes complete loss of all domains (the PH-GRAM Domain, Phosphatase Domain, Coiled-coil Domain and PDZ-Binding Motif) of the MTMR2 protein. […] The identified mutation resulted in the formation of a truncated MTMR2 protein with 39 amino acids.

• #64 MTMR2 Gene mutation causes rare Charcot-Marie-Tooth disease | TACG

  https://www.dovepress.com/identification-of-a-novel-homozygous-mutation-in-mtmr2-gene-causes-ver-peer-reviewed-fulltext-article-TACG

  CharcotMarieTooth disease (CMT) is a heterogeneous group of disorders involving peripheral nervous system. […] Germline mutations in MTMR2 gene causes CMT4B1. […] Mutations in myotubularin-related protein 2 (MTMR2), MTMR13 and MTMR5 causes CMT4B1, and CMT4B2 and CMT4B3, respectively. […] Germline mutations in MTMR2 cause CMT4B1. […] The present study reports the first mutation in the MTMR2 gene associated with CMT4B1 in a Chinese population. […] We identified a novel homozygous nonsense (c.118AT, p.Lys40*) mutation in MTMR2 in the proband. […] This mutation causes complete loss of all domains (the PH-GRAM Domain, Phosphatase Domain, Coiled-coil Domain and PDZ-Binding Motif) of the MTMR2 protein. […] The identified mutation resulted in the formation of a truncated MTMR2 protein with 39 amino acids.

• #65 Intermediate CMT | Charcot–Marie–Tooth Association

  https://www.cmtausa.org/understanding-cmt/types-of-cmt/intermediate-cmt/

  Charcot-Marie-Tooth disease, or CMT for short, is divided into three basic groups of neuropathy: demyelinating (CMT1), axonal (CMT2), and intermediate. […] The Intermediate CMT subtypes are each represented by a letter that follows the respective classification, and each are caused by mutations in different genes. […] CMTDIB is caused by an autosomal dominant mutation in the DNM2 gene […] CMTDIC is caused by an autosomal dominant mutation in the YARS1 gene […] CMTDID is caused by an autosomal dominant mutation in the MPZ gene […] CMTDIE is caused by an autosomal dominant mutation in the INF2 gene […] CMTDIF is caused by an autosomal dominant mutation in the GNB4 gene […] CMTDIG is caused by an autosomal dominant mutation in the NEFL gene […] CMTRIA is caused by an autosomal recessive mutation in the GDAP1 gene […] CMTRIB is caused by an autosomal recessive mutation in the KARS1 gene […] CMTRIC is caused by an autosomal recessive mutation in the PLEKHG5 gene […] CMTRID is caused by an autosomal recessive mutation in the COX6A1 gene.

• #66 Intermediate CMT | Charcot–Marie–Tooth Association

  https://www.cmtausa.org/understanding-cmt/types-of-cmt/intermediate-cmt/

  Charcot-Marie-Tooth disease, or CMT for short, is divided into three basic groups of neuropathy: demyelinating (CMT1), axonal (CMT2), and intermediate. […] The Intermediate CMT subtypes are each represented by a letter that follows the respective classification, and each are caused by mutations in different genes. […] CMTDIB is caused by an autosomal dominant mutation in the DNM2 gene […] CMTDIC is caused by an autosomal dominant mutation in the YARS1 gene […] CMTDID is caused by an autosomal dominant mutation in the MPZ gene […] CMTDIE is caused by an autosomal dominant mutation in the INF2 gene […] CMTDIF is caused by an autosomal dominant mutation in the GNB4 gene […] CMTDIG is caused by an autosomal dominant mutation in the NEFL gene […] CMTRIA is caused by an autosomal recessive mutation in the GDAP1 gene […] CMTRIB is caused by an autosomal recessive mutation in the KARS1 gene […] CMTRIC is caused by an autosomal recessive mutation in the PLEKHG5 gene […] CMTRID is caused by an autosomal recessive mutation in the COX6A1 gene.

• #67 Intermediate CMT | Charcot–Marie–Tooth Association

  https://www.cmtausa.org/understanding-cmt/types-of-cmt/intermediate-cmt/

  Charcot-Marie-Tooth disease, or CMT for short, is divided into three basic groups of neuropathy: demyelinating (CMT1), axonal (CMT2), and intermediate. […] The Intermediate CMT subtypes are each represented by a letter that follows the respective classification, and each are caused by mutations in different genes. […] CMTDIB is caused by an autosomal dominant mutation in the DNM2 gene […] CMTDIC is caused by an autosomal dominant mutation in the YARS1 gene […] CMTDID is caused by an autosomal dominant mutation in the MPZ gene […] CMTDIE is caused by an autosomal dominant mutation in the INF2 gene […] CMTDIF is caused by an autosomal dominant mutation in the GNB4 gene […] CMTDIG is caused by an autosomal dominant mutation in the NEFL gene […] CMTRIA is caused by an autosomal recessive mutation in the GDAP1 gene […] CMTRIB is caused by an autosomal recessive mutation in the KARS1 gene […] CMTRIC is caused by an autosomal recessive mutation in the PLEKHG5 gene […] CMTRID is caused by an autosomal recessive mutation in the COX6A1 gene.

• #68 Intermediate CMT | Charcot–Marie–Tooth Association

  https://www.cmtausa.org/understanding-cmt/types-of-cmt/intermediate-cmt/

  Charcot-Marie-Tooth disease, or CMT for short, is divided into three basic groups of neuropathy: demyelinating (CMT1), axonal (CMT2), and intermediate. […] The Intermediate CMT subtypes are each represented by a letter that follows the respective classification, and each are caused by mutations in different genes. […] CMTDIB is caused by an autosomal dominant mutation in the DNM2 gene […] CMTDIC is caused by an autosomal dominant mutation in the YARS1 gene […] CMTDID is caused by an autosomal dominant mutation in the MPZ gene […] CMTDIE is caused by an autosomal dominant mutation in the INF2 gene […] CMTDIF is caused by an autosomal dominant mutation in the GNB4 gene […] CMTDIG is caused by an autosomal dominant mutation in the NEFL gene […] CMTRIA is caused by an autosomal recessive mutation in the GDAP1 gene […] CMTRIB is caused by an autosomal recessive mutation in the KARS1 gene […] CMTRIC is caused by an autosomal recessive mutation in the PLEKHG5 gene […] CMTRID is caused by an autosomal recessive mutation in the COX6A1 gene.

• #69 Charcot-Marie-Tooth Disease – EyeWiki

  https://eyewiki.org/Charcot-Marie-Tooth_Disease

  CMT neuropathies result from inherited mutations in genes coding for myelin or axonal proteins that maintain the function of peripheral nerves. […] Over 80 genes have been linked to CMT, most commonly PMP22, MPZ, GDAP1, MFN2, GJB1, HSPB1 and HSPB8. […] Studies have revealed that approximately 90% of individuals confirmed to have CMT via molecular testing had a genetic variant in PMP22, MPZ, GDAP1, MFN2 or GJB1. […] Recent advances in technology, such as next generation sequencing (NGS), have revealed novel mutations in 7 genes associated with CMT.

• #70 A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy | PLOS Genetics

  https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005829

  Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of peripheral neuropathies with diverse genetic causes. […] The most frequent genetic cause of CMT1 is alterations in PMP22, resulting in CMT1A or CMT1E, followed by MPZ mutations, which lead to CMT1B. […] Intriguingly, mutations in Myelin basic protein (MBP) and Peripheral myelin protein 2 (PMP2), which account for 18% and 5% of peripheral myelin proteins, have not been reported as a genetic cause of CMT. […] Recently, a point mutation (p.I43N) in PMP2 was strongly suggested as a potential pathogenic mutation in a family with autosomal dominant CMT1. […] This study strongly suggests that PMP2 mutation is the underlying cause of an autosomal dominant CMT1 phenotype. […] The same mutation in PMP2 was also suggested as a strong candidate for the cause of another CMT1 family.

• #71 A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy | PLOS Genetics

  https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005829

  The PMP2 mutation cosegregated within extended family members. […] The p.I43N mutation in the PMP2 protein is located in the highly conserved lipocalin/cytosolic fatty-acid binding domain, and it was predicted to be pathogenic through several in silico analyses using SIFT, PolyPhen2, and MUpro programs. […] Therefore, the substitution may possibly alter the dynamics of the fatty acid capacitation. […] The demyelinating features were also observed in PMP2 transgenic mouse models. […] Both PMP2-WT and PMP2-I43N transgenic mice exhibited reduced MNCV, which is compatible with the CMT1 phenotype. […] Therefore, these data imply that PMP2 might result in peripheral neuropathy in the same manner as the well-characterized PMP22 gene, which affects myelination by either mutation in one allele or overdose of the wild type gene.

• #72 A novel mutation in LRSAM1 causes axonal Charcot-Marie-Tooth disease with dominant inheritance | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-14-118

  Charcot-Marie-Tooth disease (CMT) refers to a heterogeneous group of genetic motor and sensory neuropathies. […] So far, mutations in the LRSAM1 gene have been shown to cause axonal CMT in three different families and can confer either dominant or recessive transmission of the disease. […] Three different mutations in the LRSAM1 gene have been shown to cause axonal CMT in humans. […] Both mutations, p.Leu708ArgfsX28 and p.Ala683ProfsX3, disrupt the RING domain of LRSAM1. […] The underlying mutation in the LRSAM1 gene destroys the splice donor site at the 3-end of exon 25. […] This results in the insertion of 21 amino acids into the RING domain of LRSAM1 most likely rendering this domain catalytically inactive. […] CMT associated with mutations in LRSAM1 is now referred to as CMT2P, irrespective of its (dominant or recessive) mode of inheritance.

• #73 A novel mutation in LRSAM1 causes axonal Charcot-Marie-Tooth disease with dominant inheritance | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-14-118

  The absence of clinical symptoms in heterozygous carriers of the null mutation described by Guernsey et al. suggests that the other three mutations reported by Weterman et al., Nicolaou et al. and herein exert a dominant negative effect, rather than lead to haploinsufficiency. […] It is tempting to speculate that such a dominant negative effect results immediately from the disruption of the RING domain, where all three mutations occur. […] Further studies are needed to investigate if the misregulation of ESCRT complexes in LRSAM1 mutation carriers is responsible for the CMT phenotype or if other yet unknown functions of LRSAM1 also play a role.

• #74 Charcot-Marie-Tooth Disease | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/charcot-marie-tooth-disease

  Sometimes, a new genetic mutation occurs during early development, and the child develops CMT with no prior family history of the disease. […] Scientists do not know why this is the case, and it may be that CMT is just less well studied or less often diagnosed in some parts of the world, leading to these perceived differences. […] NINDS supported researchers have identified mutations in the SORD gene in people affected by a form of CMT2. […] Researchers also are learning how gene mutations in several subtypes of CMT cause problems in the protein synthesis of neurons. […] In other studies, researchers are testing nerve growth factors to prevent nerve damage.

• #75 Charcot-Marie-Tooth disease and hereditary motor neuropathies – Update 2020

  https://www.degruyter.com/document/doi/10.1515/medgen-2020-2038/html?lang=en

  Recently, biallelic SORD mutations were discovered in 38 unrelated families as the most frequent autosomal recessive form of axonal or intermediate CMT or dHMN. […] The PMP22 gene encodes the membrane glycoprotein peripheral myelin protein 22 (PMP22); proposed functions include Schwann cell maturation, myelination, myelin maintenance, and adhesion of myelin lamellae. […] Most HNPP cases result from a 1.5Mb genomic deletion encompassing the PMP22 gene the reciprocal event of the PMP22 duplication observed in CMT1A.

• #76 Charcot–Marie–Tooth disease | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg200931

  Some of these genes/mutations contribute to a significant fraction of inherited peripheral neuropathy cases and thus molecular analysis can have a substantial function in establishing a precise molecular diagnosis. […] Genetic heterogeneity, age-dependent penetrance and variable expressivity are key characteristics of CMT and related peripheral neuropathies. […] Thirty-six loci and more than two dozen genes are involved in CMT, implicating pathways in myelination, radial and axonal transport, Schwann cell differentiation, signal transduction, mitochondrial function, endosome, protein translation and single-stranded DNA break repair. […] Genotype-phenotype correlation studies suggest that genetic heterogeneity, age-dependent penetrance and variable expressivity significantly contribute to the genetics of CMT.

• #77 Charcot–Marie–Tooth disease | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg200931

  Some of these genes/mutations contribute to a significant fraction of inherited peripheral neuropathy cases and thus molecular analysis can have a substantial function in establishing a precise molecular diagnosis. […] Genetic heterogeneity, age-dependent penetrance and variable expressivity are key characteristics of CMT and related peripheral neuropathies. […] Thirty-six loci and more than two dozen genes are involved in CMT, implicating pathways in myelination, radial and axonal transport, Schwann cell differentiation, signal transduction, mitochondrial function, endosome, protein translation and single-stranded DNA break repair. […] Genotype-phenotype correlation studies suggest that genetic heterogeneity, age-dependent penetrance and variable expressivity significantly contribute to the genetics of CMT.

• #78 Charcot–Marie–Tooth disease | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg200931

  Some of these genes/mutations contribute to a significant fraction of inherited peripheral neuropathy cases and thus molecular analysis can have a substantial function in establishing a precise molecular diagnosis. […] Genetic heterogeneity, age-dependent penetrance and variable expressivity are key characteristics of CMT and related peripheral neuropathies. […] Thirty-six loci and more than two dozen genes are involved in CMT, implicating pathways in myelination, radial and axonal transport, Schwann cell differentiation, signal transduction, mitochondrial function, endosome, protein translation and single-stranded DNA break repair. […] Genotype-phenotype correlation studies suggest that genetic heterogeneity, age-dependent penetrance and variable expressivity significantly contribute to the genetics of CMT.

• #79 Charcot–Marie–Tooth disease | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg200931

  Some of these genes/mutations contribute to a significant fraction of inherited peripheral neuropathy cases and thus molecular analysis can have a substantial function in establishing a precise molecular diagnosis. […] Genetic heterogeneity, age-dependent penetrance and variable expressivity are key characteristics of CMT and related peripheral neuropathies. […] Thirty-six loci and more than two dozen genes are involved in CMT, implicating pathways in myelination, radial and axonal transport, Schwann cell differentiation, signal transduction, mitochondrial function, endosome, protein translation and single-stranded DNA break repair. […] Genotype-phenotype correlation studies suggest that genetic heterogeneity, age-dependent penetrance and variable expressivity significantly contribute to the genetics of CMT.

• #80 Charcot-Marie-Tooth Disease (CMT): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/6009-charcot-marie-tooth-disease-cmt

  Charcot-Marie-Tooth disease (CMT) is a condition that affects the nerves that control muscle movements. There are six main types of CMT, all of which happen because of a genetic mutation you inherited from one or both parents. […] CMT can involve mutations in one gene or several. So far, researchers have identified several dozen different gene mutations that can cause the different forms of CMT. […] You can have a DNA mutation in one of two ways: Inherited: These DNA mutations pass to you from one or both parents. Spontaneous: You develop these mutations while you’re still an embryo developing in the uterus. They’re sometimes called de novo mutations, which means new. […] Yes, there are seven main types of Charcot-Marie-Tooth disease, but CMT types 1 and 2 are the most common. The other forms are very or extremely rare.

• #81 Charcot–Marie–Tooth disease | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg200931

  Some of these genes/mutations contribute to a significant fraction of inherited peripheral neuropathy cases and thus molecular analysis can have a substantial function in establishing a precise molecular diagnosis. […] Genetic heterogeneity, age-dependent penetrance and variable expressivity are key characteristics of CMT and related peripheral neuropathies. […] Thirty-six loci and more than two dozen genes are involved in CMT, implicating pathways in myelination, radial and axonal transport, Schwann cell differentiation, signal transduction, mitochondrial function, endosome, protein translation and single-stranded DNA break repair. […] Genotype-phenotype correlation studies suggest that genetic heterogeneity, age-dependent penetrance and variable expressivity significantly contribute to the genetics of CMT.

• #82 Charcot-Marie-Tooth disease type 1A | MedLink Neurology

  https://www.medlink.com/articles/charcot-marie-tooth-disease-type-1a

  Inherited neuropathies are usually, though not always, inherited in an autosomal dominant pattern. Recessive forms of both demyelinating and „neuronal” forms of Charcot-Marie-Tooth disease exist. De novo PMP22 mutations are more prone to milder Charcot-Marie-Tooth disease phenotypes and are more common in children born from older fathers, suggesting that paternal age may modulate disease severity. […] Although demyelination is the pathological and physiological hallmark of Charcot-Marie-Tooth type 1, the clinical signs and symptoms of this disease, weakness and sensory loss, are probably produced by axonal degeneration and not by demyelination.

• #83 Charcot-Marie-Tooth disease (CMT) – Muscular Dystrophy UK

  https://www.musculardystrophyuk.org/conditions/a-z/charcot-marie-tooth-disease-cmt/

  An exception is CMTX, which is inherited through the X chromosome. This pattern of inheritance is called X-linked recessive. As males have only one X chromosome, and females have two, males tend to be more affected by CMTX. This also means that males can’t pass on CMTX to their male children, but affected females, even mildly, can pass it on to their male children who are likely to have more severe symptoms.

• #84 Causes of CMT – Charcot-Marie-Tooth NewsEnvelope icon

  https://charcot-marie-toothnews.com/causes-of-charcot-marie-tooth-disease-cmt/

  Charcot-Marie-Tooth disease (CMT) is a genetic disease caused by defects (or mutations) in genes that affect the function of the peripheral nerves — the nerves that control movement and sensation in the limbs. […] Mutations causing CMT are inherited either from one or both parents, or they can occur spontaneously during conception, making the child the first in the family to have the disease. […] More than 40 genes are known to be involved in CMT, with each gene linked to one or more disease subtypes. A single type of CMT can also be caused by mutations in multiple genes. The most common CMT subtype, CMT type 1A, is caused by a duplication of the PMP22 gene. […] In rare cases, CMT is caused by de novo mutations, or mutations that occur spontaneously. In such instances, neither parent is a carrier of the faulty gene, but the child still develops the disease. […] Because the different types of CMT are caused by mutations in different genes, mutations affecting more than one gene can occur at the same time in the same person. In these rare cases, this double dose of genetic changes will lead to severe symptoms.

• #85 Charcot-Marie-Tooth Disease | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/charcot-marie-tooth-disease

  Charcot-Marie-Tooth disease (CMT) is a group of genetic conditions that affect the nerves connecting the brain and spinal cord to the rest of the body. […] More than 100 genes are linked to CMT. Depending on the gene problem, CMT can affect the axon, the myelin sheath, or both. […] Although different forms of CMT involve mutations in different genes that produce proteins needed for the axon or myelin to work, all forms of CMT affect the function of peripheral nerves. Gene defects in myelin and the axons can cause them to stop working as they should, disrupting nerve signals and sometimes leading to nerve loss. […] CMT is mostly an inherited disorder, and people with a family history of Charcot-Marie-Tooth (CMT) disease are more likely to develop it. […] People inherit CMT gene mutations in three main ways: autosomal dominant, autosomal recessive, and X-linked.

• #86 Consortium Spotlight: Advancing Discoveries in Charcot-Marie-Tooth Disease | Inherited Neuropathy Consortium

  https://inc.rarediseasesnetwork.org/news/consortium-spotlight-advancing-discoveries-charcot-marie-tooth-disease

  Charcot-Marie-Tooth disease (CMT) is a rare disorder with over 100 different genetic causes and multiple subtypes. This genetic condition causes peripheral nerve dysfunction, leading to progressive disability in patients of all ages. […] Collectively, there are over 100 different genetic causes of CMT, which makes diagnosis often challengingespecially as not all genetic causes are known. […] Currently, there is no cure for any form of CMT. However, genetic identification and diagnosis is an essential first step to the potential for a cure. […] Although CMT is rare and complexas there are many different genetic causesby definition, it is a genetic disease. Therefore, the biological basis for the disease can be identified.

• #87 Consortium Spotlight: Advancing Discoveries in Charcot-Marie-Tooth Disease | Inherited Neuropathy Consortium

  https://inc.rarediseasesnetwork.org/news/consortium-spotlight-advancing-discoveries-charcot-marie-tooth-disease

  Charcot-Marie-Tooth disease (CMT) is a rare disorder with over 100 different genetic causes and multiple subtypes. This genetic condition causes peripheral nerve dysfunction, leading to progressive disability in patients of all ages. […] Collectively, there are over 100 different genetic causes of CMT, which makes diagnosis often challengingespecially as not all genetic causes are known. […] Currently, there is no cure for any form of CMT. However, genetic identification and diagnosis is an essential first step to the potential for a cure. […] Although CMT is rare and complexas there are many different genetic causesby definition, it is a genetic disease. Therefore, the biological basis for the disease can be identified.

• #88 Charcot-Marie-Tooth disease – myDr.com.au

  https://mydr.com.au/first-aid-self-care/charcot-marie-tooth-disease/

  CMT1A is the most common form of CMT accounting for at least 60 percent of all patients with CMT Type 1. It is caused by the presence of an extra copy of a gene that carries the information for making a protein called peripheral myelin protein 22 (PMP22). In these patients excessive amounts of PMP22 are produced which impairs the formation of the myelin sheath. […] More rarely, CMT is inherited in an autosomal recessive pattern which means that for an individual to develop the condition they need to inherit two altered genes one from each parent. The parents of an individual with this type of CMT each carry one copy of the altered gene, and are known as carriers, but they typically do not have symptoms of the condition. […] Understandably, the greatest is known about the most common type of CMT CMT1A which is caused by the presence of an extra copy of a gene that carries the information for making a protein called peripheral myelin protein 22 (PMP22). This results in excessive amounts of PMP22 being produced which impairs the formation of the myelin sheath. Treatment strategies currently being developed for CMT1A involve reducing the production of PMP22 protein.

• #89 Analyzing clinical and genetic aspects of axonal Charcot–Marie-Tooth disease

  https://www.e-kjgm.org/journal/view.html?doi=10.5734/JGM.2021.18.2.83

  CharcotMarie-Tooth disease (CMT) is the most common hereditary motor and sensory peripheral neuropathy. […] To date, more than 130 causative genes for CMT have been reported. […] Until now, the causative gene mutation underlying CMT could be identified in only 60% to 70% of all CMT patients, while that in the others could not be identified even by using WES. Therefore, the WGS test is needed to investigate the causative genes of those that are remaining. The cause of CMT may be a regulatory gene in the intron, a splicing mutation, copy number variation, structural variation, or transposal element. […] Accurate diagnosis based on genotype/phenotype correlation is essential in CMT2, and PGD is, therefore, widely used in CMT2 patients.

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