Materiały źródłowe

• #1 Neurofibromatosis type 2: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/neurofibromatosis-type-2/

  Neurofibromatosis type 2 is a disorder characterized by the growth of noncancerous tumors in the nervous system. […] Variants (also known as mutations) in the NF2 gene cause neurofibromatosis type 2. The NF2 gene provides instructions for making a protein called merlin (also known as schwannomin). […] Variants in the NF2 gene lead to the production of a nonfunctional version of the merlin protein that cannot regulate the growth and division of cells. Research suggests that the loss of merlin allows cells, especially Schwann cells, to multiply too frequently and form the tumors characteristic of neurofibromatosis type 2. […] Neurofibromatosis type 2 is considered to have an autosomal dominant pattern of inheritance. People with this condition are born with one altered copy of the NF2 gene in each cell. In about half of cases, the altered gene is inherited from an affected parent. The remaining cases result from new variants in the NF2 gene and occur in people with no history of the disorder in their family.

• #2

  https://europepmc.org/books/n/statpearls/article-25787/?extid=29262147&src=med

  NF2 is inherited as an autosomal dominant trait in some patients. The abnormal gene can be inherited from either of the parents, and the risk of passing the gene to offspring from a parent is 50%. […] There is no family history in some patients with NF2; the disease is caused by a de novo mutation in the NF2 gene. NF2 is caused by mutations in the NF2 gene located in the long arm of chromosome number 22 (22q12.2). The NF2 gene encodes for the protein known as merlin, which acts as a tumor suppressor gene. […] Merlin is found in the Schwann cells in the nervous system.

• #3 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  Neurofibromatosis type 2 (NF2) is inherited as an autosomal dominant condition, although half of affected individuals have NF2 as a result of a new (de novo) gene mutation. The manifestations of NF2 result from mutations in (or, rarely, deletion of) the NF2 gene, located on the long arm of chromosome 22. Affected individuals need only 1 mutated or deleted NF2 gene to exhibit signs of the condition. […] The NF2 gene product known as merlin serves as a tumor suppressor; decreased function or production of this protein results in a predisposition to develop a variety of tumors of the central and peripheral nervous systems. […] Numerous mutations in the NF2 gene have been identified, most of which are predicted to result in production of a truncated protein with loss of its usual function.

• #4 Neurofibromatosis type 2

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4748851/

  Neurofibromatosis type 2 is an autosomal-dominant multiple neoplasia syndrome that results from mutations in the NF2 tumour suppressor gene located on chromosome 22q. […] Half of patients inherit a germline mutation from an affected parent and the remainder acquire a de novo mutation for neurofibromatosis type 2. […] The NF2 tumour suppressor gene was identified in 1993. It has 17 exons that encode for a 69 kDa protein product called merlin (moesin-ezrin-radixin-like protein) or schwannomin. […] Patients either inherit a germline mutation of one affected allele from a parent or acquire a de novo mutation of an allele at the postzygotic stage of embryogenesis. […] Neurofibromatosis type 2 is an unusual inherited disorder because of the high frequency of somatic mosaicism in patients with de novo mutations.

• #5 What Is Neurofibromatosis Type 2?

  https://www.icliniq.com/articles/genetic-disorders/neurofibromatosis-type-2

  Neurofibromatosis type 2 is a genetic disorder. […] Mutation in the NF2 gene leads to this disorder. […] More than 400 mutations in the NF2 gene are seen in people with neurofibromatosis type 2. This gene mutation causes an abnormally short version of the merlin protein. The normal tumor-suppressing function is not possible in the cells, and the Schwann cell multiplies rapidly in the central nervous system.

• #6 Neurofibromatosis type 2 (NF2): A clinical and molecular review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-4-16

  Neurofibromatosis type 2 is a dominantly inherited tumour predisposition syndrome caused by mutations in the NF2 gene on chromosome 22. […] It is now clear that NF2 is a genetically homogeneous condition, with no evidence for another genetic cause of classical NF2 (bilateral VS). […] Seizinger et al. were the first to show loss of constitutional heterozygosity of chromosome 22, with DNA markers lost in tumours from a patient with NF2. […] The majority of these mutations were truncating mutations, leading to a smaller and probably non-functional protein product. […] A considerable proportion of NF2 patients, particularly milder cases, have mosaic disease, in which only a proportion of cells contain the mutated NF2 gene. […] C T transitions leading to a nonsense mutation are the most common mutations in the NF2 gene.

• #7 NF2-Related Schwannomatosis (Neurofibromatosis Type 2)

  https://my.clevelandclinic.org/health/diseases/16196-neurofibromatosis-type-2-nf2

  NF2-related schwannomatosis (neurofibromatosis type 2) is a genetic condition that affects your skin and nervous system. […] A genetic change of the neurofibromin 2 (NF 2) gene causes NF2. This is why the condition is known as NF2-related schwannomatosis. This gene helps in the production of merlin. Its a protein that stops tumors from forming (tumor-suppressor). […] You can inherit the genetic change from one of your biological parents in an autosomal dominant pattern during conception. Many people dont have a history of this genetic change in their biological family history, so they develop a new genetic change that occurs spontaneously during conception.

• #8 Neurofibromatosis: What It Is, Symptoms, Types & Treatment

  https://my.clevelandclinic.org/health/diseases/neurofibromatosis

  Neurofibromatosis is a genetic condition that affects your nervous system (brain, spinal cord and nerves) and skin. A genetic change causes this condition, which leads to unregulated tumor growth in your body. […] Neurofibromatosis (NF) is a group of neurological and genetic conditions. It causes symptoms that may affect your brain, spinal cord, nerves and skin. […] A genetic change (mutation) causes neurofibromatosis. The causes of each type are as follows: […] NF2 (merlin) is a gene that regulates another neurofibromin protein. This protein also suppresses tumors. […] When a mutation happens to one of these four genes, your proteins dont have the instructions needed to regulate cell growth, which causes tumors to form in your body. […] You can inherit NF1 or NF2 from your biological parents in an autosomal dominant pattern. This means that you only need one copy of the genetic change from one of your biological parents to develop this condition. […] Many people with NF2 also receive a spontaneous genetic mutation, and approximately 85% of schwannomatosis cases happen randomly, without a known genetic cause.

• #9 Neurofibromatosis type 2 (NF2)

  https://www.nhs.uk/conditions/neurofibromatosis-type-2/

  Neurofibromatosis type 2 (NF2) is caused by an altered gene. […] Sometimes the altered gene is passed on to a child by one of their parents (inherited), but sometimes you can be born with it even if your parents do not have the altered gene. […] If you have NF2, there’s a 1 in 2 (50%) chance of passing the affected gene on to any child you have.

• #10 Neurofibromatosis Type 2 (NF2) | American Cancer Society

  https://www.cancer.org/cancer/risk-prevention/genetics/family-cancer-syndromes/neurofibromatosis-type-2.html

  NF2 is caused by a change (mutation) in a gene called NF2. The NF2 gene, located on chromosome 22, makes a protein called merlin (also known as schwannomin). Merlin is a tumor suppressor protein and helps control cell growth. When NF2 is mutated, it can no longer make normal merlin, which allows tumors to form. […] Approximately 50% of NF2 cases are inherited from a parent, while the other 50% of cases arise from spontaneous mutation in the NF2 gene.

• #11 Neurofibromatosis Type 2 | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/neurofibromatosis-type-2

  Neurofibromatosis type 2 (NF2) is a genetic disorder that causes slow-growing tumors to develop on the eighth cranial nerve, which is located in the inner ear. […] In 50 percent of cases, NF2 is inherited from a parent. The other half of the time, NF2 occurs as a result of a spontaneous mutation. […] In 50 percent of cases, NF2 is inherited from a parent: During conception, each parent passes on a copy of the NF2 gene to the embryo. Since NF2 is an autosomal dominant genetic disorder, the child will inherit the disorder if just one of these genes has a mutation. […] In the other 50 percent of cases, NF2 occurs as a result of a spontaneous mutation: A spontaneous mutation occurs when there is a sudden change in genetic material at the time of conception. […] No, there’s no evidence suggesting that NF2 is caused by environmental factors or something the mother did (or didn’t do) during pregnancy.

• #12 Neurofibromatosis Type 2: Causes, Diagnosis, Treatment

  https://www.verywellhealth.com/neurofibromatosis-type-2-nf2-2860838

  Neurofibromatosis type 2 is a genetic disorder that causes benign (non-cancerous) tumors to grow in the nervous system. It is an autosomal dominant disorder, meaning that you can inherit the gene that causes NF2 from one parent. The genetic mutation may also occur first in the individual with the condition (called a de novo mutation). […] Neurofibromatosis type 2 is a genetic disorder with an autosomal dominant pattern. It involves a mutation of the gene located on chromosome 22, called the NF2 gene. […] With an autosomal dominant pattern, only one parent needs to contribute the gene mutation for the child to inherit the disease. In short, if one of your parents has the NF2 gene, you have a 50% chance of getting it, too. […] Also, the gene mutation can first appear in an individual (called a de novo mutation) who has no family history of neurofibromatosis type 2. […] The NF2 gene encodes the production of a protein called merlin, which can clump together around nerve cells to form benign tumors.

• #13 Neurofibromatosis Type 2 | Ento Key

  https://entokey.com/neurofibromatosis-type-2/

  Neurofibromatosis type 2 (NF2) is the official name for the syndrome whose hallmark is bilateral vestibular schwannomas (VS). […] The recent identification of the gene responsible for NF2 has significantly advanced our understanding of the molecular pathology, as well as the factors responsible for the clinical heterogeneity among patients with NF2. The NF2 gene encodes for the protein merlin or schwannomin, has been shown to have homology to the ezrinradixinmoesin family of genes, which functions as membrane-organizing proteins. […] NF2 results from the inheritance of a mutation in merlin (or schwannomin) protein on chromosome 22. […] Approximately 50% of affected patients have no family history of NF2. Therefore, these patients represent new germ line mutations in the NF2 gene. […] Although mutations in the NF2 gene play a dominant role in the biology of VS, it is also possible that other genetic loci contribute to the development of VS.

• #14 Neurofibromatosis Type 2 | St. Jude Care & Treatment

  https://www.stjude.org/care-treatment/treatment/genetic-syndromes/neurofibromatosis-type-2.html

  Neurofibromatosis type 2 (NF2) is caused by changes in the NF2 gene that make it not work correctly. The NF2 gene carries information that helps control how and when cells grow, divide, and die. […] Children who have neurofibromatosis type 2 inherit 1 normal copy of the NF2 gene and one copy that is changed (mutated). This NF2 mutation makes the gene not work correctly. As a result, it is harder for cells to control their growth and function. […] About 50% (1 in 2) of children with neurofibromatosis type 2 inherit the NF2 gene mutation from a parent who also has this disorder. The other 50% (1 in 2) of children with this disorder have a new NF2 mutation that did not come from a parent. These children have no history of the syndrome in their family. In such cases, an NF2 gene mutation happened either in: An ovum (egg) or sperm that formed the child or 1 of the child’s cells before they were born.

• #15 Neurofibromatosis: Type 2 | PM&R KnowledgeNow

  https://now.aapmr.org/neurofibromatosis-type-2/

  NF2 results from mutations in the NF2 gene on chromosome 22q12.2, encoding merlin, a tumor suppressor protein. This dysfunction can lead to tumor formation through disrupted cell growth regulation pathways such as PI3K/AKT, Raf/MEK/ERK, and mTOR. […] The disorder follows an autosomal dominant inheritance pattern, although about 50% of cases arise from spontaneous mutations (de novo mutations). […] Genetic testing identifies abnormalities of the NF2 gene on chromosome 22, altering expression of the tumor suppressor merlin. Frame shift and missense mutations are most common in familial cases. […] Significant knowledge gaps remain in managing Neurofibromatosis type 2 (NF2), especially concerning the best timing for surgical interventions and the efficacy of radiation and chemotherapy. The impact of tumor development and treatment on functional impairments is poorly understood, and the influence of rehabilitation on functional outcomes, prognosis, and quality of life requires further exploration.

• #16 Neurofibromatosis | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/neurofibromatosis

  Neurofibromatosis type 2 (NF2) is much less common than NF1. […] NF2 is caused by a faulty gene on chromosome 22. […] In people with a faulty NF2 gene, the tumour protection protein does not work as well in stopping the growth of the tumours. […] Often there is a family history of NF2 where other family members have the condition, particularly a parent. […] Where there is no family history, the condition results from a variation in the NF2 gene (mutation) that occurred for unknown reasons. […] As in NF1, these are spontaneous gene mutations. […] If the mutation occurred shortly after conception, not all the babys cells may contain the mutation the person is said to be mosaic for the faulty NF2 gene. […] The faulty gene might not be in all their egg or sperm cells, so the chance that their child will inherit the faulty gene is less than 50 per cent.

• #17 Neurofibromatosis Type 2 | St. Jude Care & Treatment

  https://www.stjude.org/care-treatment/treatment/genetic-syndromes/neurofibromatosis-type-2.html

  About 25 to 30 % of children with no family history of NF2 have mosaic neurofibromatosis 2 (sometimes called segmental neurofibromatosis 2). Mosaic means a mixture. […] A child with mosaic neurofibromatosis type 2 inherits 2 normal copies of the NF2 gene. One copy is from the mother. The other copy is from the father. But early in development, before the person is born, 1 copy of the NF2 gene becomes mutated (changed) within one cell of the developing baby. That cell keeps growing and dividing, making many more cells. All the cells that grow from that early cell will have the mutated copy of the NF2 gene. Other cells did not grow from the 1 mutated cell will have 2 normal copies of the NF2 gene. That is why it is called mosaic NF2; the person’s body is a mixture of normal cells and mutated cells.

• #18 Neurofibromatosis type 2 | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/neurofibromatosis-type-2

  In the remaining 50 percent of patients, neurofibromatosis type 2 results from the development of a new mutation in the NF2 gene in one of the fathers sperm, mothers eggs, or in a cell of the developing fetus. […] About 25 to 30 percent of individuals with no family history of neurofibromatosis type 2 are genetically mosaic for an NF2 mutation.

• #18 Neurofibromatosis type 2 | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/neurofibromatosis-type-2

  Neurofibromatosis type 2 is caused by alterations, also known as mutations, at specific areas within an individuals genetic information. […] In the vast majority of patients with neurofibromatosis type 2, the disorder develops as the result of alterations in a specific gene known as NF2, which is located on chromosome 22 at position q12.2. NF2 is the only gene known to be associated with neurofibromatosis type 2. […] Patients with neurofibromatosis type 2 generally carry an alteration in one copy of the NF2 gene in all the cells of their body. […] These tumors are believed to develop because, over time, the second working copy of the NF2 gene may become altered within one or more cells. […] Approximately 50 percent of patients with neurofibromatosis type 2 inherit an altered copy of the NF2 gene from a parent who also has neurofibromatosis type 2.

• #19 Neurofibromatosis: Types, causes, and symptoms

  https://www.medicalnewstoday.com/articles/179083

  Neurofibromatosis (Nf) is the most common genetic neurological disorder that is caused by a single gene. The mutation in the gene means that the nerve tissue is not properly controlled. […] Nf2 is a more serious condition in which tumors grow on nerves deep inside the body. […] Bilateral neurofibromatosis, or Nf2, normally stems from a mutation, rather than a deletion, of the Nf2 gene. […] Nf2 affects a similar gene on chromosome number 22. […] Both major types are passed from a parent to a child in roughly half of all known cases, and only one parent needs to have the faulty gene for a child to face a risk of developing neurofibromatosis. […] In the other half of cases, these genes will undergo what is known as a sporadic mutation in a sperm or egg cell. The causes and risk factors of sporadic mutations are unclear. […] In Nf2, the mutation can also occur after the conception of an embryo in a form called Mosaic Nf2. This is a milder form of the disease.

• #20 Neurofibromatosis type 2

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4748851/

  However, children who inherit the mutation from a mosaic parent will probably have more severe disease than will the parent because the mutation will be present in all their somatic cells. […] Although risk of transmission to offspring from parents with an inherited germline mutation has an autosomal-dominant inheritance pattern (one in two risk), the risk of transmission to the children of those with a de novo mutation is substantially lower than for the autosomal-dominant type.

• #21

  https://link.springer.com/article/10.1007/s00401-019-02029-5

  Neurofibromatosis type II (NF2) is a tumor predisposition syndrome characterized by the development of distinctive nervous system lesions. NF2 results from loss-of-function alterations in the NF2 gene on chromosome 22, with resultant dysfunction of its protein product merlin. […] NF2 is caused by inactivating alterations in the NF2 gene on chromosome 22q12.2. The 100-kb NF2 gene is encoded by 17 exons, and at least ten isoforms resulting from alternative splicing have been described in humans. […] NF2-associated tumors are thought to result when additional somatic genetic alterations in vulnerable cell populations result in bi-allelic loss of function of NF2, as per Knudsons two-hit hypothesis. However, experimental models have suggested that NF2 mutations alone may not be sufficient to promote tumorigenesis, and additional genetic alterations are likely required.

• #22 Neurofibromatosis type 2 (NF2)

  https://atlasgeneticsoncology.org/cancer-prone-disease/10007/neurofibromatosis-type-2-(nf2)

  Neurofibromatosis type 2 (NF2) is an hamartoneoplastic syndrome; hamartomas are localized tissue proliferations with faulty differenciation and mixture of component tissues; they are heritable malformations that have a potential towards neoplasia. […] Germ-line mutations in NF2 patients lead to protein truncation; splice-site or missense mutations are also found; phenotype-genotype correlations are observed (i.e. that severe phenotype are found in cases with protein truncations rather than those with amino acid substitution). […] Mutation and allele loss events in tumours in neurofibromatosis type 2 and in sporadic schwannomas and meningiomas are in accordance with the two-hit model for neoplasia.

• #23 Neurofibromatosis Type 2 Diagnosis & Treatment – NYC | Columbia Neurosurgery in New York City

  https://www.neurosurgery.columbia.edu/patient-care/conditions/neurofibromatosis-type-2

  Neurofibromatosis type 2 (NF2) is a rare genetic condition characterized by tumors in the peripheral and central nervous system. […] A mutation in the NF2 tumor-suppressor gene causes NF2. […] About half of individuals acquire the condition by inheriting a non-working NF2 gene from a parent who has NF2. (The other parent contributes a working NF2 gene.) The remaining half of individuals do not have a family history of this disease; instead, a spontaneous mutation in NF2 occurs at conception. […] NF2 is passed along in an autosomal dominant pattern, which means that if a parent has NF2, there is a 50 percent chance his or her offspring will have NF2. […] The gene NF2 is especially important to various cells in the central nervous system. In individuals with the condition NF2, each of these cells has only one working copy of the gene NF2. Recall that the other copy was inherited in a non-working state, or a mutation at conception rendered it non-working.

• #24 Neurofibromatosis Type 2 Diagnosis & Treatment – NYC | Columbia Neurosurgery in New York City

  https://www.neurosurgery.columbia.edu/patient-care/conditions/neurofibromatosis-type-2

  One working copy of the NF2 tumor suppressor gene is actually enough to keep a cell healthy. But spontaneous mutations are a usual part of cell life. When the single working copy of NF2 acquires a spontaneous mutation, there is no working copy as backupnow the cell has no working copies of the gene. A tumor begins to form.

• #25 Neurofibromatosis type 2 (NF2): A clinical and molecular review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-4-16

  There are notable similarities, but also differences between the distribution and type of germline and somatic NF2 mutations. […] Although it is thought that effectively all schwannomas require inactivation of the NF2 gene, no reports apart from those studying NF2 protein have confirmed a 100% knock out of both copies of the NF2 gene.

• #26 Current Understanding of Neurofibromatosis Type 1, 2, and Schwannomatosis

  https://www.mdpi.com/1422-0067/22/11/5850

  NF2 is caused by a defect in the gene that normally produces merlin, located at 22q12.2 of chromosome 22, which regulates multiple proliferative signaling pathways. […] The growth of schwannomas requires inactivation of both NF2 alleles. The “second hit” occurs through loss of the entire NF2 gene and most of chromosome 22. […] Various types of mutations, such as protein-truncating alterations (frameshift deletions/insertions and nonsense mutations), splice-site mutations, missense mutations, are identified. […] The presence of a truncated protein is associated with younger age at diagnosis and a higher prevalence of meningiomas, spinal tumors, and cranial nerve tumors other than VIII. […] The role of mutation screening for NF2 in all patients with a unilateral vestibular schwannoma is less certain.

• #27

  https://link.springer.com/article/10.1007/s00401-019-02029-5

  Approximately 50% of NF2 cases are suspected to result from hereditary transmission from a parent with NF2, while the remainder appear to be due to de novo mutations in patients with no known family history. An estimated 1/3 of patients with de novo NF2 mutations are mosaic for these alterations, with somatic mutations presumably occurring early in development. […] Pathogenic NF2 alterations have a nearly 100% penetrance. Approximately 50% of NF2 patients present with symptoms and/or neoplastic manifestations by the age of 20, and nearly all by the age of 60. […] Merlin interacts with the components of numerous intracellular signaling pathways including Hippo, PKA, FAK/SRC, PI3K/AKT, Rac/PAK/JNK, WNT/B-catenin, integrins, receptor tyrosine kinase (RTK), Ras, MAPK, YAP, p21-activated kinase, CD44, and Rac/Rho. […] Given its well-described role in regulating cellular proliferation in response to adhesion via multiple pathways, loss of contact-mediated growth inhibition is hypothesized to play a principal role.

• #28 Neurofibromatosis (NF) | Living With Paralysis | Reeve Foundation

  https://www.christopherreeve.org/todays-care/living-with-paralysis/health/causes-of-paralysis/neurofibromatosis/

  Neurofibromatosis 2 or NF2 (3% of cases) is characterized by tumors created by Schwann cells which are glial cells that surround neurons in the PNS. This leads to hearing loss and vestibular issues (balance, dizziness, vertigo) due to tumors on the eighth cranial nerve located in the head. NF2 is usually limited to the nervous system with only occasional skin tumors. NF2 is usually diagnosed in teens or young adults. […] Neurofibromatosis is genetic, passing from parent to child. However, some cases develop by spontaneous mutation in the genetic structure of individuals. An individual that either inherits or develops a spontaneous case of neurofibromatosis, can pass it genetically to their children. […] The genetics of neurofibromatosis is due to ineffective tumor suppression genes within the DNA of cells. The affected tumor suppression gene is different depending on the type of neurofibromatosis. Tumors can develop on the nerves and in the skin because the tumor suppression gene does not produce the effects needed to prevent overgrowth. Since the gene is not stopping tumor production, tumors can appear anywhere in the body. […] The chromosomal location of neurofibromatosis genetic effects is indicated in the following table: NF2 Chromosome 22q12 Merlin (a tumor suppression protein) related to ezrin-radixin-moesin affects the modulation or control of P13K/AKT, Raf/MEK/ERK, and mTOR signaling pathways.

• #29 Neurofibromatosis type 2 | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/neurofibromatosis-type-2-3?lang=us

  Neurofibromatosis type 2 (NF2) is a rare autosomal dominant neurocutaneous disorder (phakomatosis) manifesting as a development of multiple CNS tumors. […] Of patients with NF2, 50% have an affected parent (autosomal dominant inheritance) and 50% having a de novo mutation. […] The NF2 gene is located on the long arm of chromosome 22 (22q12) and encodes the merlin protein (also known as „schwannomin”). It plays a role in contact inhibition of growth and has tumor suppressor function at least in part according to this mechanism. […] Mutations in NF2 cause loss of protein function, resulting in a predisposition to tumor formation throughout the nervous system.

• #30 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  Neurofibromatosis type 2 (NF2) is caused by loss-of-function mutations in the NF2 gene on chromosome 22, leading the merlin protein to malfunction. […] Over half of NF2 patients have de novo mutations, and half of this group are mosaic. […] The type and severity of NF2 manifestations depend on the type of gene mutation. […] The variability within families is usually fewer than variabilities between families, implying a considerable influence of the underlying genotype. […] Evidence favors a substantial link between genotype and phenotype for NF2-related disorders. […] The types of pathogenic mutations can predict the number of intracranial meningiomas, spinal tumors, and tumors of peripheral nerves. […] The advent of molecular biology to scheme the pathogenesis of NF2 can guide to address of new therapeutic potentials for the effective prevention and treatment of NF2-related tumors.

• #31 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  NF2 is caused by loss of function mutations, deletions, or epigenetic modifications of the NF2 gene. […] The NF2 gene encodes a 70-kDa protein called merlin, mainly acting as a tumor suppressor and participating in diverse cell signaling pathways. […] Tumorigenesis occurs upon merlin loss of function by modifying downstream signaling pathways. […] The involved site also matters. Mutations in the amino-terminal domain of NF2 proteins are associated with early tumor onset with more severe disease progression. […] The Wishart phenotype, also known as the severe form, is associated with truncating mutations and alterations at the amino-terminal domain of merlin. […] In contrast, the Gardner phenotype, also known as the adult form of NF2, is associated with missense or splice site mutations, especially at the carboxy-terminal.

• #32 Neurofibromatosis Type 2 | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/1688570/0.5/Neurofibromatosis_Type_2

  NF2 is an autosomal dominant inherited tumor predisposition syndrome that predisposes affected individuals to tumors of the CNS, most commonly bilateral vestibular schwannomas, leading to hearing loss and possible deafness. […] Caused by a mutation in the NF2 gene on chromosome 22q12; autosomal dominant inheritance. […] 50% of affected patients have a new mutation. […] Historically, two forms of disease have been described: Wishart (more aggressive, onset during late teens or early 20s) and Gardner (less aggressive and older age of onset); however, many different causative mutations have been characterized. […] Severe NF2 phenotype usually caused by protein-truncating mutations (frame-shift or nonsense mutations).

• #33 Neurofibromatosis: Type 2 | PM&R KnowledgeNow

  https://now.aapmr.org/neurofibromatosis-type-2/

  An additional gap in NF2 research involves understanding the diseases immune dysregulation. Early studies indicate that NF2 patients exhibit an immunosuppressed state, with elevated cytokine levels and an abundance of immunosuppressive myeloid cells that inhibit anti-tumor responses. This emerging knowledge suggests that targeting these immune cells could lead to novel therapeutic strategies for NF2.

• #34 Neurofibromatosis – Wikipedia

  https://en.wikipedia.org/wiki/Neurofibromatosis

  The cause is a genetic mutation in certain oncogenes. These can be inherited, or in about half of cases spontaneously occur during early development. Different mutations result in the three types of NF. Neurofibromatosis arise from the supporting cells of the nervous system rather than the neurons themselves. In NF1, the tumors are neurofibromas (tumors of the peripheral nerves), while in NF2 and schwannomatosis tumors of Schwann cells are more common. […] Neurofibromatosis type II is caused by a mutation on chromosome 22 (22q12). The mutation falls on the NF2 tumor suppressor gene. The gene normally encodes a cytoplasmic protein known as merlin. The normal function of merlin is to regulate the activity of multiple growth factors, the mutated copy of the gene leads to merlin’s loss of function. The loss of function leads to increased activity of growth factors normally regulated by merlin, leading to the formation of the tumors associated with NF2.

• #35 Neurofibromatosis Type 2 – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/neurofibromatosis-type-2/

  Neurofibromatosis type 2 (NF2) is a genetic disorder that one can inherit from their parents. […] The condition known as NF2 can be inherited from parents in some patients. It acts like a dominant trait, which means only one copy of the faulty gene is needed for the disease to occur. This gene can come from either the mother or the father, and there’s a 50% chance of a parent passing on the gene to their children. […] However, not everyone with NF2 has a family history of the disease. In some cases, the disease is caused by a new mutation in the NF2 gene that wasn’t present in the genes of the parents. […] The NF2 gene is found on chromosome number 22 and its role is to provide instructions for making a protein called merlin. This protein acts as a tumor suppressor, which means it helps control cell growth and prevent tumors from forming. Specifically, merlin is found in special cells called Schwann cells, which are part of the nervous system. When the NF2 gene is faulty, this can lead to the development of NF2. […] Neurofibromatosis Type 2 (NF2) can be inherited from parents or caused by a new mutation in the NF2 gene.

• #36 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  The clinical manifestations of NF2 are in a wide range, from no symptoms to life-threatening symptoms, depending on the involved nerves. […] The bilateral VS is the hallmark feature of NF2 that originate from myelin-forming Schwann cells in the vestibulocochlear nerve. […] The significant impacts of NF2 on the patients quality of life and the severity of symptoms urge the need to explore effective therapies. […] The multifocal nature of NF2-related tumors, their proximity to the vital structures, or neural involvement can limit surgical interventions. […] In patients with NF2, radiotherapy can increase the risk of developing additional benign tumors in the irradiated field and malignant transformation of existing benign tumors. […] The available systemic therapies are limited to a handful of choices with limited efficacy. […] Exploring its genetic and epigenetic backgrounds and the involved signaling pathways can help to find better treatments.

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