Materiały źródłowe

• #1 Huntington’s disease – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/huntingtons-disease/symptoms-causes/syc-20356117

  Huntington’s disease is caused by a difference in a single gene that’s passed down from a parent. Huntington’s disease follows an autosomal dominant inheritance pattern. This means that a person needs only one copy of the nontypical gene to develop the disorder. […] People who have a parent with Huntington’s disease are at risk of having the disease themselves. Children of a parent with Huntington’s have a 50 percent chance of having the gene change that causes Huntington’s.

• #2 Huntington’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Huntington%27s_disease

  Huntington’s disease (HD), also known as Huntington’s chorea, is an incurable neurodegenerative disease that is mostly inherited. […] HD is typically inherited from an affected parent, who carries a mutation in the huntingtin gene (HTT). However, up to 10% of cases are due to a new mutation. […] The huntingtin gene provides the genetic information for huntingtin protein (Htt). Expansion of CAG repeats of cytosine-adenine-guanine (known as a trinucleotide repeat expansion) in the gene coding for the huntingtin protein results in an abnormal mutant protein (mHtt), which gradually damages brain cells through a number of possible mechanisms. […] The Huntington’s disease mutation is genetically dominant and almost fully penetrant; mutation of either of a person’s HTT alleles causes the disease.

• #3 Huntington’s Disease: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/14369-huntingtons-disease

  Huntingtons disease is an inherited condition that causes brain cells to slowly lose function and die. […] A genetic change (mutation) of the HTT gene causes Huntingtons disease. The HTT gene makes a protein called huntingtin. This protein helps your nerve cells (neurons) function. […] If you have Huntingtons disease, your DNA doesnt have all the information needed to make the huntingtin protein. As a result, these proteins grow in an abnormal shape and destroy (instead of help) your neurons. Your neurons die because of this genetic mutation. […] Yes, you can inherit the genetic change (mutation) that causes Huntingtons disease. You can develop this condition if one of your biological parents carries the genetic change and passes it on to you. This is an autosomal dominant pattern of inheritance. […] Anyone can develop Huntingtons disease, but its most common if someone in your biological family has the condition. If one of your parents has Huntingtons disease, you have a 50% chance of also developing it.

• #4 Huntington’s disease

  https://www.nhs.uk/conditions/huntingtons-disease/diagnosis/

  Huntington’s disease is an inherited genetic condition. It’s caused by an altered gene being passed on to a child by one of their parents. […] Having the altered gene causes damage to certain areas of your brain. This affects your movement, memory and thinking. […] If one of your parents carries the altered gene, there’s a 1 in 2 (50%) chance that you will have the gene and develop Huntington’s disease.

• #5 Huntington Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559166/

  Huntington disease is a hereditary neurodegenerative disorder, inherited in an autosomal dominant manner, caused by an expansion of CAG trinucleotide repeats in the HTT gene on chromosome 4p16.3, leading to an abnormal polyglutamine expansion in the huntingtin protein. […] Huntington disease is an autosomal dominant inherited neurodegenerative disorder caused by the elongation of CAG repeats on the short arm of chromosome 4p16.3 in the HTT gene. […] The gene encodes for the HTT protein, which plays a crucial role in synaptic function in the postembryonic period. […] Patients commonly have the HTT allele with CAG repeats in the range of 36 to 55. […] Those with juvenile-onset of the disease usually have CAG repeats greater than 60. […] A repeat length of 36 to 39 may result in the development of Huntington disease, yet not in all cases, ie, reduced penetrance.

• #6 Huntington’s Disease | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/huntingtons-disease

  Huntington’s disease (HD) is an inherited disorder that causes nerve cells (neurons) in parts of the brain to gradually break down and die. […] HD is caused by a mutation in the gene for a protein called Huntingtin. The defect causes the building blocks of DNA called cytosine, adenine, and guanine (CAG) to repeat many more times than they normally do. […] Most people have fewer than 27 CAG repeats in their HD gene, so they are not at risk for the disease. People who have CAG repeats in the middle range (27 to 35) are not likely to develop the disease, but they could still pass it on to future generations. People with HD may have 36 or more CAG repeats. […] When a parent has HD, each child has a 50% chance of inheriting the copy of chromosome 4 that carries the HD mutation. If a child does not inherit the HD mutation, he or she will not develop the disease and cannot pass it on to future generations. When HD occurs without a family history, it is called sporadic HD.

• #7 Huntington’s Disease Association – What causes Huntington’s disease

  https://www.hda.org.uk/information-and-support/huntingtons-disease/what-causes-huntingtons-disease/

  Huntingtons disease is a genetic disease, which means if you have it, you inherited it from one or both of your parents. It is caused by a hereditary fault on a specific gene. […] The gene that causes Huntingtons is often called the huntingtin gene (HTT). It is attached to chromosome number four. It produces an important protein, called huntingtin, which is needed by nerve cells in the brain (neurons) and for the bodys development before birth. […] When the huntingtin gene is faulty, the huntingtin protein it produces repeats certain genetic sequences known as CAG (cytosine-adenine-guanine) too many times. This in turn appears to damage neurons in certain areas of the brain – although how and why this happens is not yet fully understood. […] The faulty gene that causes Huntingtons repeats a particular coding sequence known as CAG (cytosine-adenine-guanine) too many times – a bit like adding too much of one ingredient in a recipe. This means the protein it makes damages nerve cells in the brain.

• #8 Huntington Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559166/

  Huntington disease is a hereditary neurodegenerative disorder, inherited in an autosomal dominant manner, caused by an expansion of CAG trinucleotide repeats in the HTT gene on chromosome 4p16.3, leading to an abnormal polyglutamine expansion in the huntingtin protein. […] Huntington disease is an autosomal dominant inherited neurodegenerative disorder caused by the elongation of CAG repeats on the short arm of chromosome 4p16.3 in the HTT gene. […] The gene encodes for the HTT protein, which plays a crucial role in synaptic function in the postembryonic period. […] Patients commonly have the HTT allele with CAG repeats in the range of 36 to 55. […] Those with juvenile-onset of the disease usually have CAG repeats greater than 60. […] A repeat length of 36 to 39 may result in the development of Huntington disease, yet not in all cases, ie, reduced penetrance.

• #9 Huntington’s Disease | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/huntingtons-disease

  Huntington’s disease (HD) is an inherited disorder that causes nerve cells (neurons) in parts of the brain to gradually break down and die. […] HD is caused by a mutation in the gene for a protein called Huntingtin. The defect causes the building blocks of DNA called cytosine, adenine, and guanine (CAG) to repeat many more times than they normally do. […] Most people have fewer than 27 CAG repeats in their HD gene, so they are not at risk for the disease. People who have CAG repeats in the middle range (27 to 35) are not likely to develop the disease, but they could still pass it on to future generations. People with HD may have 36 or more CAG repeats. […] When a parent has HD, each child has a 50% chance of inheriting the copy of chromosome 4 that carries the HD mutation. If a child does not inherit the HD mutation, he or she will not develop the disease and cannot pass it on to future generations. When HD occurs without a family history, it is called sporadic HD.

• #10 Huntington Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1150165-overview

  Huntington disease (HD) is an incurable, adult-onset, autosomal dominant inherited disorder associated with cell loss within a specific subset of neurons in the basal ganglia and cortex. […] The genetic basis of HD is the expansion of a cysteine-adenosine-guanine (CAG) repeat encoding a polyglutamine tract in the N-terminus of the protein product called huntingtin. […] Several mechanisms of neuronal cell death have been proposed for HD, including excitotoxicity, oxidative stress, impaired energy metabolism, and apoptosis. […] NMDA receptors are depleted in the striata of patients with HD, suggesting a role of NMDA receptor-mediated excitotoxicity, but no correlation exists between the distribution of neuronal loss and the density of such receptors. […] Oxidative stress is caused by the presence of free radicals (ie, highly reactive oxygen derivatives) in large amounts.

• #11 Huntington’s Disease: Symptoms, Causes & Support

  https://www.healthline.com/health/huntingtons-disease

  Huntingtons disease is a hereditary condition that gradually breaks down your brains nerve cells, affecting your physical movements, emotions, and cognitive abilities. […] A defect in a single gene, the huntingtin (HTT) gene, causes Huntingtons disease. That said, the genetic mutation is different from many other mutations. There isnt a substitution or a missing section in the gene. Instead, theres a copying error. […] Specifically, a section of the genetic code within this gene called the cytosine-adenine-guanine (CAG) trinucleotide is copied too many times. The number of repeated copies tends to increase with each generation. […] Huntingtons is considered an autosomal dominant disorder. This means that one copy of the abnormal gene is enough to cause the disease. If one of your parents has this genetic defect, you have a 50% chance of inheriting it. You can also pass it on to your children.

• #12 Huntington’s Disease | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/huntingtons-disease

  Huntington’s disease (HD) is an inherited disorder that causes nerve cells (neurons) in parts of the brain to gradually break down and die. […] HD is caused by a mutation in the gene for a protein called Huntingtin. The defect causes the building blocks of DNA called cytosine, adenine, and guanine (CAG) to repeat many more times than they normally do. […] Most people have fewer than 27 CAG repeats in their HD gene, so they are not at risk for the disease. People who have CAG repeats in the middle range (27 to 35) are not likely to develop the disease, but they could still pass it on to future generations. People with HD may have 36 or more CAG repeats. […] When a parent has HD, each child has a 50% chance of inheriting the copy of chromosome 4 that carries the HD mutation. If a child does not inherit the HD mutation, he or she will not develop the disease and cannot pass it on to future generations. When HD occurs without a family history, it is called sporadic HD.

• #13 Huntington’s disease: Symptoms, causes, and treatment

  https://www.medicalnewstoday.com/articles/159552

  Huntingtons disease (HD) is an inherited neurological condition that happens when a gene mutation causes toxic proteins to collect in different parts of the brain. […] HD results from a gene mutation on chromosome 4 of huntingtin (HTT). […] This genetic mutation is caused by the excessive production or trinucleotide repeats of cytosine, adenine, and guanine (CAG). […] Normally, CAG repeats 36 times or less. But, in HD it repeats 36 times or more. […] This change results in a longer form of the HTT protein, which is then cut into small harmful cells that could bind together. As the toxic protein accumulates in the brain, it begins to damage certain brain cells. This causes symptoms. […] If the repetition is 36-39, a person may or may not develop HD. If it repeats 40 times or more, a person will almost certainly develop the condition.

• #14 Huntington’s Disease | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/huntingtons-disease

  Huntington’s disease (HD) is an inherited disorder that causes nerve cells (neurons) in parts of the brain to gradually break down and die. […] HD is caused by a mutation in the gene for a protein called Huntingtin. The defect causes the building blocks of DNA called cytosine, adenine, and guanine (CAG) to repeat many more times than they normally do. […] Most people have fewer than 27 CAG repeats in their HD gene, so they are not at risk for the disease. People who have CAG repeats in the middle range (27 to 35) are not likely to develop the disease, but they could still pass it on to future generations. People with HD may have 36 or more CAG repeats. […] When a parent has HD, each child has a 50% chance of inheriting the copy of chromosome 4 that carries the HD mutation. If a child does not inherit the HD mutation, he or she will not develop the disease and cannot pass it on to future generations. When HD occurs without a family history, it is called sporadic HD.

• #15 Huntington disease: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000770.htm

  Huntington disease (HD) is a genetic disorder in which nerve cells in certain parts of the brain waste away, or degenerate. The disease is passed down through families. […] HD is caused by a genetic defect on chromosome 4. The defect causes a part of your DNA to occur many more times than it is supposed to. This defect is called a CAG repeat. Normally, this section of DNA is repeated 10 to 28 times. But in people with HD, it is repeated 36 to 120 times. […] As the gene is passed down through families, the number of repeats tends to get larger. The larger the number of repeats, the higher a person’s chance of developing symptoms at an earlier age. Therefore, as the disease is passed along in families, symptoms develop at younger and younger ages. […] If one of your parents has HD, you have a 50% chance of getting the gene. If you get the gene from your parents, you can pass it on to your children, who will also have a 50% chance of getting the gene. If you do not get the gene from your parents, you cannot pass the gene on to your children.

• #16 Huntington’s Disease | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/huntingtons-disease

  Huntington’s disease (HD) is an inherited disorder that causes nerve cells (neurons) in parts of the brain to gradually break down and die. […] HD is caused by a mutation in the gene for a protein called Huntingtin. The defect causes the building blocks of DNA called cytosine, adenine, and guanine (CAG) to repeat many more times than they normally do. […] Most people have fewer than 27 CAG repeats in their HD gene, so they are not at risk for the disease. People who have CAG repeats in the middle range (27 to 35) are not likely to develop the disease, but they could still pass it on to future generations. People with HD may have 36 or more CAG repeats. […] When a parent has HD, each child has a 50% chance of inheriting the copy of chromosome 4 that carries the HD mutation. If a child does not inherit the HD mutation, he or she will not develop the disease and cannot pass it on to future generations. When HD occurs without a family history, it is called sporadic HD.

• #17 Huntington’s disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/huntingtons-disease/

  As the altered HTT gene is passed from one generation to the next, the size of the CAG trinucleotide repeat often increases in size. […] Individuals who have 27 to 35 CAG repeats in the HTT gene do not develop Huntington’s disease, but they are at risk of having children who will develop the disorder.

• #18 Huntington’s disease: Symptoms, causes, and treatment

  https://www.medicalnewstoday.com/articles/159552

  Huntingtons disease (HD) is an inherited neurological condition that happens when a gene mutation causes toxic proteins to collect in different parts of the brain. […] HD results from a gene mutation on chromosome 4 of huntingtin (HTT). […] This genetic mutation is caused by the excessive production or trinucleotide repeats of cytosine, adenine, and guanine (CAG). […] Normally, CAG repeats 36 times or less. But, in HD it repeats 36 times or more. […] This change results in a longer form of the HTT protein, which is then cut into small harmful cells that could bind together. As the toxic protein accumulates in the brain, it begins to damage certain brain cells. This causes symptoms. […] If the repetition is 36-39, a person may or may not develop HD. If it repeats 40 times or more, a person will almost certainly develop the condition.

• #19 About Huntington’s Disease – European Huntington’s Disease Network

  https://ehdn.org/about-hd/

  As the number of CAG repeats increases, that particular section of DNA becomes more unstable. This means that the number of repeats in this section can increase or decrease when it is passed down to the next generation. As long as the number of CAG repeats in the HTT gene is lower than 27, the section is stable. If the number of repeats is between 27 and 35 (the so-called intermediate repeat length), that individual will not develop HD and the section is considered normal. However, a CAG repeat number of 27 or more is unstable and liable to increase when passed on to the next generation, meaning that those children carry a risk of developing HD. Individuals with a CAG repeat number between 36 and 39 may develop HD, but only very late in life, if at all. This is known as the reduced-penetrance repeat length range. When the number of CAG repeats is higher than 39, a person will develop HD within a normal lifespan most often in mid-adult life. In rare cases the CAG expansion can be exceptionally long, leading to disease onset in adolescence or childhood (juvenile HD). Patients who develop the disease before the age of 10 often have more than 80 CAG repeats.

• #20 Huntington Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559166/

  A repeat length of 40 is almost always completely penetrant and will result in Huntington disease symptomatology. […] Similar to other trinucleotide (triplet) repeat inherited disorders, a phenomenon of anticipation occurs. […] Studies have found 3 significant categories of risk factors for the onset of the disease. The CAG repeat lengths in the HTT gene, instability of CAG, and genetic modifiers were identified as risk factors.

• #21 Huntington’s Disease Association – What causes Huntington’s disease

  https://www.hda.org.uk/information-and-support/huntingtons-disease/what-causes-huntingtons-disease/

  If you have 40 or more CAG repeats, it is certain that you will develop Huntingtons at some point. […] More than 50 CAG repeats, it is highly likely that you will get Juvenile Huntingtons (in other words, you will start to experience symptoms before the age of 20). But not everyone with a high CAG count develops Juvenile Huntingtons. […] If you do have more than 50 repeats, there is a 90% chance you got the faulty gene from your father as CAG repeats tend to be more unstable when passed on from the man.

• #22 Huntington Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559166/

  Huntington disease is a hereditary neurodegenerative disorder, inherited in an autosomal dominant manner, caused by an expansion of CAG trinucleotide repeats in the HTT gene on chromosome 4p16.3, leading to an abnormal polyglutamine expansion in the huntingtin protein. […] Huntington disease is an autosomal dominant inherited neurodegenerative disorder caused by the elongation of CAG repeats on the short arm of chromosome 4p16.3 in the HTT gene. […] The gene encodes for the HTT protein, which plays a crucial role in synaptic function in the postembryonic period. […] Patients commonly have the HTT allele with CAG repeats in the range of 36 to 55. […] Those with juvenile-onset of the disease usually have CAG repeats greater than 60. […] A repeat length of 36 to 39 may result in the development of Huntington disease, yet not in all cases, ie, reduced penetrance.

• #23 Huntington’s Disease Association – What causes Huntington’s disease

  https://www.hda.org.uk/information-and-support/huntingtons-disease/what-causes-huntingtons-disease/

  If you have 40 or more CAG repeats, it is certain that you will develop Huntingtons at some point. […] More than 50 CAG repeats, it is highly likely that you will get Juvenile Huntingtons (in other words, you will start to experience symptoms before the age of 20). But not everyone with a high CAG count develops Juvenile Huntingtons. […] If you do have more than 50 repeats, there is a 90% chance you got the faulty gene from your father as CAG repeats tend to be more unstable when passed on from the man.

• #24 Huntington’s Disease Etiology | Medically Roche

  https://medically.roche.com/global/en/microsites/huntingtons-disease/pathology-and-mechanisms.html

  Huntingtons disease (HD) is caused by a cytosineadenineguanine (CAG) trinucleotide repeat expansion in the huntingtin gene (HTT); a gain-of-function mutation leading to the production of toxic mutant huntingtin (mHTT) protein.1 The degree of symptom severity, disease stage, and markers of neuronal damage have been shown to correlate with levels of the mHTT protein in the cerebrospinal fluid in individuals with HD. […] The production of this toxic mutant huntingtin protein leads to progressive neuronal degeneration, ultimately leading to neuronal cell death.5 Levels of mHTT protein in cerebrospinal fluid have been shown to correlate with disease stage, symptom severity and markers of neuronal damage in people with HD.5 […] Researchers identified that the number of CAG trinucleotide repeat expansions in the huntingtin gene (HTT) has been shown to correlate with the age of disease onset.2,3 It is known that a CAG repeat length of 40 results in definite HD,1,7-10 CAG repeat length inversely correlates with age of onset,3,7 and other genetic and environmental factors may also affect disease progression.3,11

• #25 Huntington’s Disease Causes | Huntington’s Disease NewsEnvelope icon

  https://huntingtonsdiseasenews.com/huntingtons-disease-causes/

  The underlying cause of Huntington’s disease, which is characterized by a progressive decline in movement, cognition, and mental stability, is a mutation in a gene called huntingtin (HTT). […] The defect in the HTT gene responsible for Huntington’s disease is known as a CAG trinucleotide repeat expansion. […] Normally, the HTT gene CAG trinucleotide repeat contains 10 to 35 repeats of this sequence. In people with Huntington’s disease, however, it may be repeated from 36 to more than 120 times. […] The number of repeats inversely correlates with the age of onset of the disease. […] The CAG trinucleotide repeat expansion in the gene results in a longer-than-usual huntingtin protein being produced. This abnormal protein is thought to form clumps in neurons, which disrupt the normal function of these cells and eventually cause their death.

• #26 Overview of Huntington’s Disease – Huntington’s Disease Society of America

  https://hdsa.org/what-is-hd/overview-of-huntingtons-disease/

  HD affects the whole brain, but certain areas are more vulnerable than others. Huntington’s disease (HD) is a brain disease that is passed down in families from generation to generation. It is caused by a mistake in the DNA instructions that build our bodies and keep them running. […] The DNA error that causes HD is found in a gene called huntingtin. This gene was discovered in 1993. Everyone has the huntingtin gene, but only those that inherit the mistake, known as the HD mutation, will develop HD and risk passing it on to their children. […] HD is caused by a stretch of the letters C-A-G in the huntingtin gene which repeat over and over, too many times…CAGCAGCAGCAGCAG. This is known as a CAG repeat expansion. […] The extra CAG repeats in people with HD cause the huntingtin protein to be extra-long and difficult to maintain, which makes it difficult for it to do its job. Over many years, this “mutant” huntingtin protein forms clumps in brain cells, and causes them to become damaged and die. The most vulnerable part of the brain in HD is called the striatum, and it controls movement, mood, and memory. Damage to the striatum over time is what causes the symptoms of HD.

• #27 Overview of Huntington’s Disease – Huntington’s Disease Society of America

  https://hdsa.org/what-is-hd/overview-of-huntingtons-disease/

  HD affects the whole brain, but certain areas are more vulnerable than others. Huntington’s disease (HD) is a brain disease that is passed down in families from generation to generation. It is caused by a mistake in the DNA instructions that build our bodies and keep them running. […] The DNA error that causes HD is found in a gene called huntingtin. This gene was discovered in 1993. Everyone has the huntingtin gene, but only those that inherit the mistake, known as the HD mutation, will develop HD and risk passing it on to their children. […] HD is caused by a stretch of the letters C-A-G in the huntingtin gene which repeat over and over, too many times…CAGCAGCAGCAGCAG. This is known as a CAG repeat expansion. […] The extra CAG repeats in people with HD cause the huntingtin protein to be extra-long and difficult to maintain, which makes it difficult for it to do its job. Over many years, this “mutant” huntingtin protein forms clumps in brain cells, and causes them to become damaged and die. The most vulnerable part of the brain in HD is called the striatum, and it controls movement, mood, and memory. Damage to the striatum over time is what causes the symptoms of HD.

• #28 Huntington’s disease – symptoms, treatments and causes | healthdirect

  https://www.healthdirect.gov.au/huntingtons-disease

  Huntington’s disease is an inherited condition that affects the nervous system. […] Huntington’s disease is caused by a faulty gene that someone is born with. […] Huntington’s disease is caused by a faulty gene you are born with. A person only needs to inherit the gene from one parent to be affected by Huntington’s disease. […] Huntington’s disease results in the death of brain cells. The parts of the brain affected are the frontal lobe and basal ganglia. These are responsible for movement, thinking, personality and emotions.

• #29 Huntington Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559166/

  A repeat length of 40 is almost always completely penetrant and will result in Huntington disease symptomatology. […] Similar to other trinucleotide (triplet) repeat inherited disorders, a phenomenon of anticipation occurs. […] Studies have found 3 significant categories of risk factors for the onset of the disease. The CAG repeat lengths in the HTT gene, instability of CAG, and genetic modifiers were identified as risk factors.

• #30 Huntington disease: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000770.htm

  Huntington disease (HD) is a genetic disorder in which nerve cells in certain parts of the brain waste away, or degenerate. The disease is passed down through families. […] HD is caused by a genetic defect on chromosome 4. The defect causes a part of your DNA to occur many more times than it is supposed to. This defect is called a CAG repeat. Normally, this section of DNA is repeated 10 to 28 times. But in people with HD, it is repeated 36 to 120 times. […] As the gene is passed down through families, the number of repeats tends to get larger. The larger the number of repeats, the higher a person’s chance of developing symptoms at an earlier age. Therefore, as the disease is passed along in families, symptoms develop at younger and younger ages. […] If one of your parents has HD, you have a 50% chance of getting the gene. If you get the gene from your parents, you can pass it on to your children, who will also have a 50% chance of getting the gene. If you do not get the gene from your parents, you cannot pass the gene on to your children.

• #31 Huntington’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Huntington%27s_disease

  The length of the trinucleotide repeat accounts for 60% of the variation of the age of symptoms onset and their rate of progress. A longer repeat results in an earlier age of onset and a faster progression of symptoms. […] The remaining variation is due to environmental factors and other genes that influence the mechanism of the disease.

• #32 Huntington Disease – Neurologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/neurologic-disorders/movement-and-cerebellar-disorders/huntington-disease

  Huntington disease results from a mutation in the huntingtin (HTT) gene (on chromosome 4), causing abnormal repetition of the DNA sequence CAG, which codes for the amino acid glutamine. The resulting gene product, a large protein called huntingtin, has an expanded stretch of polyglutamine residues, which accumulate within neurons and lead to disease via unknown mechanisms. The more CAG repeats, the earlier the onset of disease and the more severe its expression (phenotype). The number of CAG repeats can increase with successive generations when the father transmits the mutation and, over time, can lead to increasingly severe phenotypes within a family (called anticipation). […] Diagnosis of Huntington disease is based on typical symptoms and signs plus a positive family history. It is confirmed by genetic testing that measures the number of CAG repeats. […] Therapies currently under study aim to reduce glutamatergic neurotransmission via the N-methyl-d-aspartate receptor and to bolster mitochondrial energy production. Treatments that aim to increase GABAergic function in the brain have been ineffective.

• #33 Huntington’s Disease Association – What causes Huntington’s disease

  https://www.hda.org.uk/information-and-support/huntingtons-disease/what-causes-huntingtons-disease/

  If you have 40 or more CAG repeats, it is certain that you will develop Huntingtons at some point. […] More than 50 CAG repeats, it is highly likely that you will get Juvenile Huntingtons (in other words, you will start to experience symptoms before the age of 20). But not everyone with a high CAG count develops Juvenile Huntingtons. […] If you do have more than 50 repeats, there is a 90% chance you got the faulty gene from your father as CAG repeats tend to be more unstable when passed on from the man.

• #34 Surprise finding sheds light on what causes Huntington’s disease, a devastating fatal brain disorder | AP News

  https://apnews.com/article/huntingtons-disease-harvard-mit-genetic-involuntary-movement-b87b387b4ea37e41b43f4f9952b89117

  Scientists are unraveling the mystery of what triggers Huntingtons disease, a devastating and fatal hereditary disorder that strikes in the prime of life, causing nerve cells in parts of the brain to break down and die. […] The genetic mutation linked to Huntingtons has long been known, but scientists havent understood how people could have the mutation from birth, but not develop any problems until later in life. […] New research shows that the mutation is, surprisingly, harmless for decades. But it quietly grows into a larger mutation until it eventually crosses a threshold, generates toxic proteins, and kills the cells it has expanded in. […] They focused on the Huntingtons mutation, which involves a stretch of DNA in a particular gene where a three-letter sequence CAG is repeated at least 40 times. In people without the disease this sequence is repeated just 15 to 35 times. They discovered that DNA tracts with 40 or more such repeats expand over time until they are hundreds of CAGs long. Once CAGs reach a threshold of about 150, certain types of neurons sicken and die.

• #35 Surprising way that genetic mutation causes Huntington’s disease changes understanding of the disorder

  https://medicalxpress.com/news/2025-01-genetic-mutation-huntington-disease-disorder.html

  Scientists at the Broad Institute of MIT and Harvard, Harvard Medical School, and McLean Hospital have discovered a surprising mechanism by which the inherited genetic mutation known to cause Huntington’s disease leads to the death of brain cells. […] For 30 years, researchers have known that Huntington’s is caused by an inherited mutation in the Huntingtin (HTT) gene, but they didn’t know how the mutation causes brain cell death. […] A study published in Cell reveals that the inherited mutation doesn’t itself harm cells. Rather, the mutation is innocuous for decades but slowly morphs into a highly toxic form that then quickly kills the cell. […] The Huntington’s mutation involves a stretch of DNA in the HTT gene in which a three-letter sequence of DNA, „CAG,” is repeated at least 40 times, as opposed to the 15-35 repeats inherited by people without the disease.

• #36 Surprise finding sheds light on what causes Huntington’s disease, a devastating fatal brain disorder | AP News

  https://apnews.com/article/huntingtons-disease-harvard-mit-genetic-involuntary-movement-b87b387b4ea37e41b43f4f9952b89117

  Scientists are unraveling the mystery of what triggers Huntingtons disease, a devastating and fatal hereditary disorder that strikes in the prime of life, causing nerve cells in parts of the brain to break down and die. […] The genetic mutation linked to Huntingtons has long been known, but scientists havent understood how people could have the mutation from birth, but not develop any problems until later in life. […] New research shows that the mutation is, surprisingly, harmless for decades. But it quietly grows into a larger mutation until it eventually crosses a threshold, generates toxic proteins, and kills the cells it has expanded in. […] They focused on the Huntingtons mutation, which involves a stretch of DNA in a particular gene where a three-letter sequence CAG is repeated at least 40 times. In people without the disease this sequence is repeated just 15 to 35 times. They discovered that DNA tracts with 40 or more such repeats expand over time until they are hundreds of CAGs long. Once CAGs reach a threshold of about 150, certain types of neurons sicken and die.

• #37 Study finds surprising way that genetic mutation causes Huntington’s disease, transforming understanding of the disorder | Broad Institute

  https://www.broadinstitute.org/news/study-finds-surprising-way-genetic-mutation-causes-huntingtons-disease-transforming

  Researchers studying brain cells from Huntingtons patients show that the mutation, which changes over decades, becomes toxic only later in life. Scientists at the Broad Institute of MIT and Harvard, Harvard Medical School, and McLean Hospital have discovered a surprising mechanism by which the inherited genetic mutation known to cause Huntingtons disease leads to the death of brain cells. For 30 years, researchers have known that Huntingtons is caused by an inherited mutation in the Huntingtin (HTT) gene, but they didnt know how the mutation causes brain cell death. A new study published today in Cell reveals that the inherited mutation doesnt itself harm cells. Rather, the mutation is innocuous for decades but slowly morphs into a highly toxic form that then quickly kills the cell. The Huntingtons mutation involves a stretch of DNA in the HTT gene in which a three-letter sequence of DNA, CAG, is repeated at least 40 times, as opposed to the 15-35 repeats inherited by people without the disease. Only once a cell’s DNA expansion reaches a threshold number of CAGs roughly 150 does the cell sicken and then die. The cumulative death of many such cells leads to the symptoms of Huntingtons disease. In 1993, researchers discovered that the disease is caused by an expanded stretch of CAGs in the HTT gene. Most people inherit versions of the gene with 15 to 35 consecutive CAGs and never develop Huntingtons, but those who inherit a version with 40 or more consecutive CAGs almost always develop the illness later in life. The longer the stretch of repeats, the younger a person tends to be when symptoms first appear. But underlying biological questions had always lingered: How is the HTT mutation toxic? Why would the HTT protein which appears in almost every cell in the body kill only some brain cells and not others? And why do patients, who are born with the mutation and express the protein throughout life, develop symptoms only in middle age, after decades of apparent good health? The researchers found that CAG-repeat tracts initially grow slowly, expanding less than once a year during the first two decades of life. But when a cell’s repeat tract reaches about 80 CAGs usually after several decades its rate of expansion accelerates dramatically and it expands to 150 CAGs in only a few more years. The cell then dies just months later. This means that a neuron spends more than 95 percent of its life with an innocuous HTT gene. McCarrolls team suggests that rather than targeting the HTT protein, a complementary or potentially better therapeutic approach could be to slow or stop the DNA-repeat expansion, which could help delay or even prevent the disease.

• #38 Study finds surprising way that genetic mutation causes Huntington’s disease, transforming understanding of the disorder | Broad Institute

  https://www.broadinstitute.org/news/study-finds-surprising-way-genetic-mutation-causes-huntingtons-disease-transforming

  Researchers studying brain cells from Huntingtons patients show that the mutation, which changes over decades, becomes toxic only later in life. Scientists at the Broad Institute of MIT and Harvard, Harvard Medical School, and McLean Hospital have discovered a surprising mechanism by which the inherited genetic mutation known to cause Huntingtons disease leads to the death of brain cells. For 30 years, researchers have known that Huntingtons is caused by an inherited mutation in the Huntingtin (HTT) gene, but they didnt know how the mutation causes brain cell death. A new study published today in Cell reveals that the inherited mutation doesnt itself harm cells. Rather, the mutation is innocuous for decades but slowly morphs into a highly toxic form that then quickly kills the cell. The Huntingtons mutation involves a stretch of DNA in the HTT gene in which a three-letter sequence of DNA, CAG, is repeated at least 40 times, as opposed to the 15-35 repeats inherited by people without the disease. Only once a cell’s DNA expansion reaches a threshold number of CAGs roughly 150 does the cell sicken and then die. The cumulative death of many such cells leads to the symptoms of Huntingtons disease. In 1993, researchers discovered that the disease is caused by an expanded stretch of CAGs in the HTT gene. Most people inherit versions of the gene with 15 to 35 consecutive CAGs and never develop Huntingtons, but those who inherit a version with 40 or more consecutive CAGs almost always develop the illness later in life. The longer the stretch of repeats, the younger a person tends to be when symptoms first appear. But underlying biological questions had always lingered: How is the HTT mutation toxic? Why would the HTT protein which appears in almost every cell in the body kill only some brain cells and not others? And why do patients, who are born with the mutation and express the protein throughout life, develop symptoms only in middle age, after decades of apparent good health? The researchers found that CAG-repeat tracts initially grow slowly, expanding less than once a year during the first two decades of life. But when a cell’s repeat tract reaches about 80 CAGs usually after several decades its rate of expansion accelerates dramatically and it expands to 150 CAGs in only a few more years. The cell then dies just months later. This means that a neuron spends more than 95 percent of its life with an innocuous HTT gene. McCarrolls team suggests that rather than targeting the HTT protein, a complementary or potentially better therapeutic approach could be to slow or stop the DNA-repeat expansion, which could help delay or even prevent the disease.

• #39 Huntington’s Disease: Causes and Risk Factors | Banner Health

  https://www.bannerhealth.com/services/neurology/programs-care/movement-disorders/huntingtons-disease/causes-and-risk-factors

  Huntingtons disease is inherited, meaning its passed down from parents to children. It follows an autosomal dominant inheritance pattern. This means that a person only needs to inherit one copy of the mutated HTT gene from a parent to develop the disease. […] Each child of a parent with Huntingtons disease has a 50% chance of inheriting the faulty gene. If they inherit it, they will eventually develop the disease. If they do not inherit the mutation, they will not get Huntingtons and cannot pass it on to their own children. The disease does not skip generations. […] The biggest risk factor for Huntingtons disease is having a parent with the condition. If one of your parents has it, you are at risk of inheriting the gene. […] Some other factors that may influence when symptoms begin or how quickly they progress include: The exact number of CAG repeats in the HTT gene, Environmental influences, such as diet and lifestyle, Other genetic variations that researchers are still studying.

• #40 Huntington’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Huntington%27s_disease

  The length of the trinucleotide repeat accounts for 60% of the variation of the age of symptoms onset and their rate of progress. A longer repeat results in an earlier age of onset and a faster progression of symptoms. […] The remaining variation is due to environmental factors and other genes that influence the mechanism of the disease.

• #41 Huntington Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559166/

  A repeat length of 40 is almost always completely penetrant and will result in Huntington disease symptomatology. […] Similar to other trinucleotide (triplet) repeat inherited disorders, a phenomenon of anticipation occurs. […] Studies have found 3 significant categories of risk factors for the onset of the disease. The CAG repeat lengths in the HTT gene, instability of CAG, and genetic modifiers were identified as risk factors.

• #42 Huntington Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559166/

  A repeat length of 40 is almost always completely penetrant and will result in Huntington disease symptomatology. […] Similar to other trinucleotide (triplet) repeat inherited disorders, a phenomenon of anticipation occurs. […] Studies have found 3 significant categories of risk factors for the onset of the disease. The CAG repeat lengths in the HTT gene, instability of CAG, and genetic modifiers were identified as risk factors.

• #43 Huntington Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559166/

  A repeat length of 40 is almost always completely penetrant and will result in Huntington disease symptomatology. […] Similar to other trinucleotide (triplet) repeat inherited disorders, a phenomenon of anticipation occurs. […] Studies have found 3 significant categories of risk factors for the onset of the disease. The CAG repeat lengths in the HTT gene, instability of CAG, and genetic modifiers were identified as risk factors.

• #44 Huntington’s Disease: Causes and Risk Factors | Banner Health

  https://www.bannerhealth.com/services/neurology/programs-care/movement-disorders/huntingtons-disease/causes-and-risk-factors

  Huntingtons disease is inherited, meaning its passed down from parents to children. It follows an autosomal dominant inheritance pattern. This means that a person only needs to inherit one copy of the mutated HTT gene from a parent to develop the disease. […] Each child of a parent with Huntingtons disease has a 50% chance of inheriting the faulty gene. If they inherit it, they will eventually develop the disease. If they do not inherit the mutation, they will not get Huntingtons and cannot pass it on to their own children. The disease does not skip generations. […] The biggest risk factor for Huntingtons disease is having a parent with the condition. If one of your parents has it, you are at risk of inheriting the gene. […] Some other factors that may influence when symptoms begin or how quickly they progress include: The exact number of CAG repeats in the HTT gene, Environmental influences, such as diet and lifestyle, Other genetic variations that researchers are still studying.

• #45 Huntington’s Disease Association – What causes Huntington’s disease

  https://www.hda.org.uk/information-and-support/huntingtons-disease/what-causes-huntingtons-disease/

  If you have 40 or more CAG repeats, it is certain that you will develop Huntingtons at some point. […] More than 50 CAG repeats, it is highly likely that you will get Juvenile Huntingtons (in other words, you will start to experience symptoms before the age of 20). But not everyone with a high CAG count develops Juvenile Huntingtons. […] If you do have more than 50 repeats, there is a 90% chance you got the faulty gene from your father as CAG repeats tend to be more unstable when passed on from the man.

• #46 Huntington’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Huntington%27s_disease

  The length of the trinucleotide repeat accounts for 60% of the variation of the age of symptoms onset and their rate of progress. A longer repeat results in an earlier age of onset and a faster progression of symptoms. […] The remaining variation is due to environmental factors and other genes that influence the mechanism of the disease.

• #47 Huntington’s Disease: Symptoms, Causes & Support

  https://www.healthline.com/health/huntingtons-disease

  In general, symptoms of Huntingtons disease show up earlier in people with a larger number of repeats. The disease also progresses faster as more repeats build up. […] Your genetics determines whether or not you will develop Huntingtons. However, some factors can influence the time of onset and how the condition progresses. […] Research also suggests that environmental factors like stress, your level of physical activity, toxins youre exposed to, and your diet may speed up or slow the progression of the disease.

• #48 Huntington’s Disease: Symptoms, Causes & Support

  https://www.healthline.com/health/huntingtons-disease

  In general, symptoms of Huntingtons disease show up earlier in people with a larger number of repeats. The disease also progresses faster as more repeats build up. […] Your genetics determines whether or not you will develop Huntingtons. However, some factors can influence the time of onset and how the condition progresses. […] Research also suggests that environmental factors like stress, your level of physical activity, toxins youre exposed to, and your diet may speed up or slow the progression of the disease.

• #49 Huntington’s Disease: Symptoms, Causes & Support

  https://www.healthline.com/health/huntingtons-disease

  In general, symptoms of Huntingtons disease show up earlier in people with a larger number of repeats. The disease also progresses faster as more repeats build up. […] Your genetics determines whether or not you will develop Huntingtons. However, some factors can influence the time of onset and how the condition progresses. […] Research also suggests that environmental factors like stress, your level of physical activity, toxins youre exposed to, and your diet may speed up or slow the progression of the disease.

• #50 Huntington’s Disease: Symptoms, Causes & Support

  https://www.healthline.com/health/huntingtons-disease

  In general, symptoms of Huntingtons disease show up earlier in people with a larger number of repeats. The disease also progresses faster as more repeats build up. […] Your genetics determines whether or not you will develop Huntingtons. However, some factors can influence the time of onset and how the condition progresses. […] Research also suggests that environmental factors like stress, your level of physical activity, toxins youre exposed to, and your diet may speed up or slow the progression of the disease.

• #51 Huntington’s Disease: Symptoms, Causes & Support

  https://www.healthline.com/health/huntingtons-disease

  In general, symptoms of Huntingtons disease show up earlier in people with a larger number of repeats. The disease also progresses faster as more repeats build up. […] Your genetics determines whether or not you will develop Huntingtons. However, some factors can influence the time of onset and how the condition progresses. […] Research also suggests that environmental factors like stress, your level of physical activity, toxins youre exposed to, and your diet may speed up or slow the progression of the disease.

• #52 Huntington’s Disease: Causes and Risk Factors | Banner Health

  https://www.bannerhealth.com/services/neurology/programs-care/movement-disorders/huntingtons-disease/causes-and-risk-factors

  Huntingtons disease is inherited, meaning its passed down from parents to children. It follows an autosomal dominant inheritance pattern. This means that a person only needs to inherit one copy of the mutated HTT gene from a parent to develop the disease. […] Each child of a parent with Huntingtons disease has a 50% chance of inheriting the faulty gene. If they inherit it, they will eventually develop the disease. If they do not inherit the mutation, they will not get Huntingtons and cannot pass it on to their own children. The disease does not skip generations. […] The biggest risk factor for Huntingtons disease is having a parent with the condition. If one of your parents has it, you are at risk of inheriting the gene. […] Some other factors that may influence when symptoms begin or how quickly they progress include: The exact number of CAG repeats in the HTT gene, Environmental influences, such as diet and lifestyle, Other genetic variations that researchers are still studying.

• #53 Huntington Disease Causes and Diagnoses | Northwestern Medicine

  https://www.nm.org/conditions-and-care-areas/neurosciences/movement-disorders/huntingtons-disease/causes-and-diagnoses

  Huntington’s disease (HD) is a genetic disorder passed on from parents to children. If a parent has HD, the child has a 50 percent chance of developing it too. […] One to three percent of people with HD have no family history of the disorder. […] Blood tests, specifically genetic testing, can determine the likelihood of developing Huntingtons disease.

• #54 Huntington’s Disease | Conditions | UCSF Health

  https://www.ucsfhealth.org/conditions/huntingtons-disease

  Huntington’s disease (HD) is a fatal condition typically characterized by involuntary movements and dementia. The disease is caused by genetically programmed degeneration of brain cells, called neurons, in certain areas of the brain. […] The disease is a hereditary disorder passed on by a parent to child through a mutation in a gene. […] Children of parents with Huntington’s disease have a 50 percent chance of inheriting the HD gene. If a child does not inherit the gene, he or she won’t develop the disease and can’t pass it on. A person who inherits the HD gene will eventually develop the disease. […] In 1 to 3 percent of individuals with HD, there is no family history of the disease. […] Currently, there is no cure for Huntington’s disease and no treatment to slow its progression. Treatments are available, however, to help control the symptoms. […] Studies are being conducted to determine if antioxidants and other agents help protect the brain and prevent degeneration in HD. So far, these studies have not shown any benefit.

• #55 Huntington’s disease | NHS inform

  https://www.nhsinform.scot/illnesses-and-conditions/brain-nerves-and-spinal-cord/huntingtons-disease/

  Huntingtons disease is caused by a faulty gene. Cells in parts of the brain are very sensitive to the effects of the faulty gene. This makes them function poorly and eventually die. […] A parent with the Huntingtons disease gene has one good copy of the gene and one faulty copy. […] In around 3% of cases of Huntingtons disease, theres no obvious family history of the condition. This could be because relatives with the condition died before they were diagnosed with it. In rare cases, its due to a new fault in the gene that causes Huntingtons disease.

• #56 Huntington’s Disease Association of Ireland – What is Huntington’s Disease?

  https://www.huntingtons.ie/What-is-Huntingtons-Disease

  Huntingtons disease (HD) is a neurological illness caused by an expanded gene in your DNA. The faulty HD gene causes cells in parts of your brain to gradually malfunction and die. […] Huntington’s Disease is hereditary. Each child conceived naturally to a parent who carries the HD gene has a 50% chance of inheriting or not inheriting the illness. If you inherit the HD gene you will develop the illness at some stage in your life and your children will have a 50% risk. If you do not inherit the gene you will not develop symptoms nor can you pass the illness to your children. […] Some people develop Huntingtons disease without ever knowing they were at risk. This may be explained by a parents misdiagnosis, the early death of a parent before symptoms appeared, adoption or mistaken paternity. On rare occasions it can be caused by the random expansion of a normal parental gene.

• #57 Huntington’s Disease Association of Ireland – What is Huntington’s Disease?

  https://www.huntingtons.ie/What-is-Huntingtons-Disease

  Huntingtons disease (HD) is a neurological illness caused by an expanded gene in your DNA. The faulty HD gene causes cells in parts of your brain to gradually malfunction and die. […] Huntington’s Disease is hereditary. Each child conceived naturally to a parent who carries the HD gene has a 50% chance of inheriting or not inheriting the illness. If you inherit the HD gene you will develop the illness at some stage in your life and your children will have a 50% risk. If you do not inherit the gene you will not develop symptoms nor can you pass the illness to your children. […] Some people develop Huntingtons disease without ever knowing they were at risk. This may be explained by a parents misdiagnosis, the early death of a parent before symptoms appeared, adoption or mistaken paternity. On rare occasions it can be caused by the random expansion of a normal parental gene.

• #58 Huntington’s disease | NHS inform

  https://www.nhsinform.scot/illnesses-and-conditions/brain-nerves-and-spinal-cord/huntingtons-disease/

  Huntingtons disease is caused by a faulty gene. Cells in parts of the brain are very sensitive to the effects of the faulty gene. This makes them function poorly and eventually die. […] A parent with the Huntingtons disease gene has one good copy of the gene and one faulty copy. […] In around 3% of cases of Huntingtons disease, theres no obvious family history of the condition. This could be because relatives with the condition died before they were diagnosed with it. In rare cases, its due to a new fault in the gene that causes Huntingtons disease.

• #59 DZNE

  https://www.dzne.de/en/news/background/huntingtons-disease/

  Huntington’s disease is genetic and inherited in an autosomal dominant manner. […] The cause of the disease is a genetic defect. […] A region on chromosome number four is affected. […] Here, there is an area where the DNA building blocks CAG (cytosine, adenine, and guanine) repeat themselves several times – in most people between 10 and 30 times. […] After about 36 repetitions the disease gets clinically apparent. […] The number of repetitions might increase from one generation to the next. […] The rule of thumb is that the more CAGs, the earlier the onset of the disease and the more rapidly it progresses. […] Approximately one to three percent of all affected individuals have no known family history of Huntington’s chorea. […] In these cases, either it may be a spontaneous alteration in the genetic material or the number of repetitions has exceeded a critical limit from one generation to the next.

• #60 Huntington Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1150165-overview

  Huntington disease (HD) is an incurable, adult-onset, autosomal dominant inherited disorder associated with cell loss within a specific subset of neurons in the basal ganglia and cortex. […] The genetic basis of HD is the expansion of a cysteine-adenosine-guanine (CAG) repeat encoding a polyglutamine tract in the N-terminus of the protein product called huntingtin. […] Several mechanisms of neuronal cell death have been proposed for HD, including excitotoxicity, oxidative stress, impaired energy metabolism, and apoptosis. […] NMDA receptors are depleted in the striata of patients with HD, suggesting a role of NMDA receptor-mediated excitotoxicity, but no correlation exists between the distribution of neuronal loss and the density of such receptors. […] Oxidative stress is caused by the presence of free radicals (ie, highly reactive oxygen derivatives) in large amounts.

• #61 Huntington disease: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/huntington-disease-clinical-features-and-diagnosis

  Huntington disease (HD) is an inherited progressive neurodegenerative disorder characterized by choreiform movements, psychiatric problems, and dementia. It is caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the huntingtin (HTT) gene on chromosome 4p and inherited in an autosomal dominant pattern. […] The pathophysiology of HD is not fully understood, although it is thought to be related to toxicity of the mutant huntingtin protein.

• #62 Huntington Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1150165-overview

  Huntington disease (HD) is an incurable, adult-onset, autosomal dominant inherited disorder associated with cell loss within a specific subset of neurons in the basal ganglia and cortex. […] The genetic basis of HD is the expansion of a cysteine-adenosine-guanine (CAG) repeat encoding a polyglutamine tract in the N-terminus of the protein product called huntingtin. […] Several mechanisms of neuronal cell death have been proposed for HD, including excitotoxicity, oxidative stress, impaired energy metabolism, and apoptosis. […] NMDA receptors are depleted in the striata of patients with HD, suggesting a role of NMDA receptor-mediated excitotoxicity, but no correlation exists between the distribution of neuronal loss and the density of such receptors. […] Oxidative stress is caused by the presence of free radicals (ie, highly reactive oxygen derivatives) in large amounts.

• #63 Huntington Disease – Neurologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/neurologic-disorders/movement-and-cerebellar-disorders/huntington-disease

  Huntington disease results from a mutation in the huntingtin (HTT) gene (on chromosome 4), causing abnormal repetition of the DNA sequence CAG, which codes for the amino acid glutamine. The resulting gene product, a large protein called huntingtin, has an expanded stretch of polyglutamine residues, which accumulate within neurons and lead to disease via unknown mechanisms. The more CAG repeats, the earlier the onset of disease and the more severe its expression (phenotype). The number of CAG repeats can increase with successive generations when the father transmits the mutation and, over time, can lead to increasingly severe phenotypes within a family (called anticipation). […] Diagnosis of Huntington disease is based on typical symptoms and signs plus a positive family history. It is confirmed by genetic testing that measures the number of CAG repeats. […] Therapies currently under study aim to reduce glutamatergic neurotransmission via the N-methyl-d-aspartate receptor and to bolster mitochondrial energy production. Treatments that aim to increase GABAergic function in the brain have been ineffective.

• #64 Huntington Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1150165-overview

  Huntington disease (HD) is an incurable, adult-onset, autosomal dominant inherited disorder associated with cell loss within a specific subset of neurons in the basal ganglia and cortex. […] The genetic basis of HD is the expansion of a cysteine-adenosine-guanine (CAG) repeat encoding a polyglutamine tract in the N-terminus of the protein product called huntingtin. […] Several mechanisms of neuronal cell death have been proposed for HD, including excitotoxicity, oxidative stress, impaired energy metabolism, and apoptosis. […] NMDA receptors are depleted in the striata of patients with HD, suggesting a role of NMDA receptor-mediated excitotoxicity, but no correlation exists between the distribution of neuronal loss and the density of such receptors. […] Oxidative stress is caused by the presence of free radicals (ie, highly reactive oxygen derivatives) in large amounts.

• #65 Huntington Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1150165-overview

  Impaired energy metabolism reduces the threshold for glutamate toxicity and can lead to activation of excitotoxic mechanisms as well as increased production of reactive oxygen species. […] One theory is that expanded polyglutamine repeats cause neuronal degeneration through abnormal interactions with other proteins containing short polyglutamine tracts.

• #66 Huntington Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1150165-overview

  Huntington disease (HD) is an incurable, adult-onset, autosomal dominant inherited disorder associated with cell loss within a specific subset of neurons in the basal ganglia and cortex. […] The genetic basis of HD is the expansion of a cysteine-adenosine-guanine (CAG) repeat encoding a polyglutamine tract in the N-terminus of the protein product called huntingtin. […] Several mechanisms of neuronal cell death have been proposed for HD, including excitotoxicity, oxidative stress, impaired energy metabolism, and apoptosis. […] NMDA receptors are depleted in the striata of patients with HD, suggesting a role of NMDA receptor-mediated excitotoxicity, but no correlation exists between the distribution of neuronal loss and the density of such receptors. […] Oxidative stress is caused by the presence of free radicals (ie, highly reactive oxygen derivatives) in large amounts.

• #67 Huntington Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1150165-overview

  Impaired energy metabolism reduces the threshold for glutamate toxicity and can lead to activation of excitotoxic mechanisms as well as increased production of reactive oxygen species. […] One theory is that expanded polyglutamine repeats cause neuronal degeneration through abnormal interactions with other proteins containing short polyglutamine tracts.

• #68 Huntington’s disease gene also enhances early brain development and intelligence | Carver College of Medicine

  https://medicine.uiowa.edu/content/huntingtons-disease-gene-also-enhances-early-brain-development-and-intelligence

  Although surprising, the findings are in line with studies from evolutionary biologists who believe that genes like HTT may have been „positively selected” for human brain evolution. This theory, known as antagonistic pleiotropy, suggests that certain genes can produce a beneficial effect early in life, but come at a cost later in life. […] Overall, our study suggests that we should rethink the notion of the toxic protein theory. Instead, we should consider the theory of antagonistic pleiotropy—a theory that suggests that genes like HTT build a better brain early in life, but the cost of the superior brain is that it isn’t built to last and may be prone to premature or accelerating aging.

• #69 Huntington’s disease gene also enhances early brain development and intelligence | Carver College of Medicine

  https://medicine.uiowa.edu/content/huntingtons-disease-gene-also-enhances-early-brain-development-and-intelligence

  Gene mutation appears to confer early benefit despite later cost. The genetic mutation that causes Huntingtons disease (HD) a devastating brain disease that disrupts mobility and diminishes cognitive ability may also enhance early brain development and play a role in promoting human intelligence. […] Huntingtons disease is caused by a mutation in the huntingtin (HTT) gene. The protein produced by the HTT gene is necessary for normal development, but variations within a segment of the protein have a profound effect on the brain. […] We know that the expanded gene causes a horrible degenerative disease later in life, but we also know it is a gene that is crucial for general development. […] The finding suggests that early in life, the gene mutation is actually beneficial to brain development, but that early benefit later becomes a liability.

• #70 Huntington’s disease gene also enhances early brain development and intelligence | Carver College of Medicine

  https://medicine.uiowa.edu/content/huntingtons-disease-gene-also-enhances-early-brain-development-and-intelligence

  Gene mutation appears to confer early benefit despite later cost. The genetic mutation that causes Huntingtons disease (HD) a devastating brain disease that disrupts mobility and diminishes cognitive ability may also enhance early brain development and play a role in promoting human intelligence. […] Huntingtons disease is caused by a mutation in the huntingtin (HTT) gene. The protein produced by the HTT gene is necessary for normal development, but variations within a segment of the protein have a profound effect on the brain. […] We know that the expanded gene causes a horrible degenerative disease later in life, but we also know it is a gene that is crucial for general development. […] The finding suggests that early in life, the gene mutation is actually beneficial to brain development, but that early benefit later becomes a liability.

• #71 Huntington’s disease gene also enhances early brain development and intelligence | Carver College of Medicine

  https://medicine.uiowa.edu/content/huntingtons-disease-gene-also-enhances-early-brain-development-and-intelligence

  Although surprising, the findings are in line with studies from evolutionary biologists who believe that genes like HTT may have been „positively selected” for human brain evolution. This theory, known as antagonistic pleiotropy, suggests that certain genes can produce a beneficial effect early in life, but come at a cost later in life. […] Overall, our study suggests that we should rethink the notion of the toxic protein theory. Instead, we should consider the theory of antagonistic pleiotropy—a theory that suggests that genes like HTT build a better brain early in life, but the cost of the superior brain is that it isn’t built to last and may be prone to premature or accelerating aging.

• #72 Surprising way that genetic mutation causes Huntington’s disease changes understanding of the disorder

  https://medicalxpress.com/news/2025-01-genetic-mutation-huntington-disease-disorder.html

  This type of „somatic expansion” occurs in only the specific types of brain cells that later die in Huntington’s disease. Only once a cell’s DNA expansion reaches a threshold number of CAGs—roughly 150—does the cell sicken and then die. The cumulative death of many such cells leads to the symptoms of Huntington’s disease. […] The study offers a potential explanation as to why candidate Huntington’s drugs that aim to reduce expression of the HTT protein have struggled in clinical trials: Very few cells have the toxic version of the protein at any given time, so the treatments may not be having a therapeutic effect in most cells. […] McCarroll’s team suggests that rather than targeting the HTT protein, a complementary or potentially better therapeutic approach could be to slow or stop the DNA-repeat expansion, which could help delay or even prevent the disease. […] More than 50 human brain disorders, including fragile X syndrome and myotonic dystrophy, are caused by expansions of DNA repeats in various genes.

• #73 Surprising way that genetic mutation causes Huntington’s disease changes understanding of the disorder

  https://medicalxpress.com/news/2025-01-genetic-mutation-huntington-disease-disorder.html

  This type of „somatic expansion” occurs in only the specific types of brain cells that later die in Huntington’s disease. Only once a cell’s DNA expansion reaches a threshold number of CAGs—roughly 150—does the cell sicken and then die. The cumulative death of many such cells leads to the symptoms of Huntington’s disease. […] The study offers a potential explanation as to why candidate Huntington’s drugs that aim to reduce expression of the HTT protein have struggled in clinical trials: Very few cells have the toxic version of the protein at any given time, so the treatments may not be having a therapeutic effect in most cells. […] McCarroll’s team suggests that rather than targeting the HTT protein, a complementary or potentially better therapeutic approach could be to slow or stop the DNA-repeat expansion, which could help delay or even prevent the disease. […] More than 50 human brain disorders, including fragile X syndrome and myotonic dystrophy, are caused by expansions of DNA repeats in various genes.

• #74 Surprise finding sheds light on what causes Huntington’s disease, a devastating fatal brain disorder | AP News

  https://apnews.com/article/huntingtons-disease-harvard-mit-genetic-involuntary-movement-b87b387b4ea37e41b43f4f9952b89117

  The longer the repeats, the earlier in life the onset will happen, said neuroscience researcher Sabina Berretta, one of the studys senior authors. […] Researchers acknowledged that some scientists were initially skeptical when results were shared at conferences, since previous work found that repeat expansions in the range of 30 to 100 CAGs were necessary but not sufficient to cause Huntingtons. McCarroll agreed that 100 or fewer CAGs are not sufficient to trigger the disease, but said his study found that expansions with at least 150 CAGs are. […] Researchers hope their findings can help scientists come up with ways to delay or prevent the incurable condition, which afflicts about 41,000 Americans and is now treated with medications to manage the symptoms. […] Slowing or stopping the expansion of DNA repeats may be a better way to target the disease, researchers said.

• #75 Surprising way that genetic mutation causes Huntington’s disease changes understanding of the disorder

  https://medicalxpress.com/news/2025-01-genetic-mutation-huntington-disease-disorder.html

  This type of „somatic expansion” occurs in only the specific types of brain cells that later die in Huntington’s disease. Only once a cell’s DNA expansion reaches a threshold number of CAGs—roughly 150—does the cell sicken and then die. The cumulative death of many such cells leads to the symptoms of Huntington’s disease. […] The study offers a potential explanation as to why candidate Huntington’s drugs that aim to reduce expression of the HTT protein have struggled in clinical trials: Very few cells have the toxic version of the protein at any given time, so the treatments may not be having a therapeutic effect in most cells. […] McCarroll’s team suggests that rather than targeting the HTT protein, a complementary or potentially better therapeutic approach could be to slow or stop the DNA-repeat expansion, which could help delay or even prevent the disease. […] More than 50 human brain disorders, including fragile X syndrome and myotonic dystrophy, are caused by expansions of DNA repeats in various genes.

• #76 Huntington Disease – Neurologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/neurologic-disorders/movement-and-cerebellar-disorders/huntington-disease

  Huntington disease results from a mutation in the huntingtin (HTT) gene (on chromosome 4), causing abnormal repetition of the DNA sequence CAG, which codes for the amino acid glutamine. The resulting gene product, a large protein called huntingtin, has an expanded stretch of polyglutamine residues, which accumulate within neurons and lead to disease via unknown mechanisms. The more CAG repeats, the earlier the onset of disease and the more severe its expression (phenotype). The number of CAG repeats can increase with successive generations when the father transmits the mutation and, over time, can lead to increasingly severe phenotypes within a family (called anticipation). […] Diagnosis of Huntington disease is based on typical symptoms and signs plus a positive family history. It is confirmed by genetic testing that measures the number of CAG repeats. […] Therapies currently under study aim to reduce glutamatergic neurotransmission via the N-methyl-d-aspartate receptor and to bolster mitochondrial energy production. Treatments that aim to increase GABAergic function in the brain have been ineffective.

• #77 Huntington Disease – Neurologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/neurologic-disorders/movement-and-cerebellar-disorders/huntington-disease

  Huntington disease results from a mutation in the huntingtin (HTT) gene (on chromosome 4), causing abnormal repetition of the DNA sequence CAG, which codes for the amino acid glutamine. The resulting gene product, a large protein called huntingtin, has an expanded stretch of polyglutamine residues, which accumulate within neurons and lead to disease via unknown mechanisms. The more CAG repeats, the earlier the onset of disease and the more severe its expression (phenotype). The number of CAG repeats can increase with successive generations when the father transmits the mutation and, over time, can lead to increasingly severe phenotypes within a family (called anticipation). […] Diagnosis of Huntington disease is based on typical symptoms and signs plus a positive family history. It is confirmed by genetic testing that measures the number of CAG repeats. […] Therapies currently under study aim to reduce glutamatergic neurotransmission via the N-methyl-d-aspartate receptor and to bolster mitochondrial energy production. Treatments that aim to increase GABAergic function in the brain have been ineffective.

• #78 Huntington’s disease | UK DRI

  https://www.ukdri.ac.uk/conditions/huntingtons-disease

  Prof Vincent Dion is harnessing CRISPR technology to edit genes directly and has shown in exciting proof-of-concept studies that he is able to ‘contract’ the expanded CAG repeat region in Huntington’s which could slow the progression of Huntington’s disease. […] Another promising area of research for Huntington’s disease relates to mechanisms of DNA repair which are thought to go wrong in the condition.

• #79 Huntington’s disease | UK DRI

  https://www.ukdri.ac.uk/conditions/huntingtons-disease

  Prof Vincent Dion is harnessing CRISPR technology to edit genes directly and has shown in exciting proof-of-concept studies that he is able to ‘contract’ the expanded CAG repeat region in Huntington’s which could slow the progression of Huntington’s disease. […] Another promising area of research for Huntington’s disease relates to mechanisms of DNA repair which are thought to go wrong in the condition.

• #80 Surprising way that genetic mutation causes Huntington’s disease changes understanding of the disorder

  https://medicalxpress.com/news/2025-01-genetic-mutation-huntington-disease-disorder.html

  This type of „somatic expansion” occurs in only the specific types of brain cells that later die in Huntington’s disease. Only once a cell’s DNA expansion reaches a threshold number of CAGs—roughly 150—does the cell sicken and then die. The cumulative death of many such cells leads to the symptoms of Huntington’s disease. […] The study offers a potential explanation as to why candidate Huntington’s drugs that aim to reduce expression of the HTT protein have struggled in clinical trials: Very few cells have the toxic version of the protein at any given time, so the treatments may not be having a therapeutic effect in most cells. […] McCarroll’s team suggests that rather than targeting the HTT protein, a complementary or potentially better therapeutic approach could be to slow or stop the DNA-repeat expansion, which could help delay or even prevent the disease. […] More than 50 human brain disorders, including fragile X syndrome and myotonic dystrophy, are caused by expansions of DNA repeats in various genes.

• #81 Huntington’s disease – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/huntingtons-disease/symptoms-causes/syc-20356117

  Huntington’s disease is caused by a difference in a single gene that’s passed down from a parent. Huntington’s disease follows an autosomal dominant inheritance pattern. This means that a person needs only one copy of the nontypical gene to develop the disorder. […] People who have a parent with Huntington’s disease are at risk of having the disease themselves. Children of a parent with Huntington’s have a 50 percent chance of having the gene change that causes Huntington’s.

• #82 Huntington Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559166/

  Huntington disease is a hereditary neurodegenerative disorder, inherited in an autosomal dominant manner, caused by an expansion of CAG trinucleotide repeats in the HTT gene on chromosome 4p16.3, leading to an abnormal polyglutamine expansion in the huntingtin protein. […] Huntington disease is an autosomal dominant inherited neurodegenerative disorder caused by the elongation of CAG repeats on the short arm of chromosome 4p16.3 in the HTT gene. […] The gene encodes for the HTT protein, which plays a crucial role in synaptic function in the postembryonic period. […] Patients commonly have the HTT allele with CAG repeats in the range of 36 to 55. […] Those with juvenile-onset of the disease usually have CAG repeats greater than 60. […] A repeat length of 36 to 39 may result in the development of Huntington disease, yet not in all cases, ie, reduced penetrance.

• #83 Overview of Huntington’s Disease – Huntington’s Disease Society of America

  https://hdsa.org/what-is-hd/overview-of-huntingtons-disease/

  HD affects the whole brain, but certain areas are more vulnerable than others. Huntington’s disease (HD) is a brain disease that is passed down in families from generation to generation. It is caused by a mistake in the DNA instructions that build our bodies and keep them running. […] The DNA error that causes HD is found in a gene called huntingtin. This gene was discovered in 1993. Everyone has the huntingtin gene, but only those that inherit the mistake, known as the HD mutation, will develop HD and risk passing it on to their children. […] HD is caused by a stretch of the letters C-A-G in the huntingtin gene which repeat over and over, too many times…CAGCAGCAGCAGCAG. This is known as a CAG repeat expansion. […] The extra CAG repeats in people with HD cause the huntingtin protein to be extra-long and difficult to maintain, which makes it difficult for it to do its job. Over many years, this “mutant” huntingtin protein forms clumps in brain cells, and causes them to become damaged and die. The most vulnerable part of the brain in HD is called the striatum, and it controls movement, mood, and memory. Damage to the striatum over time is what causes the symptoms of HD.

• #84 Huntington’s Disease Etiology | Medically Roche

  https://medically.roche.com/global/en/microsites/huntingtons-disease/pathology-and-mechanisms.html

  Huntingtons disease (HD) is caused by a cytosineadenineguanine (CAG) trinucleotide repeat expansion in the huntingtin gene (HTT); a gain-of-function mutation leading to the production of toxic mutant huntingtin (mHTT) protein.1 The degree of symptom severity, disease stage, and markers of neuronal damage have been shown to correlate with levels of the mHTT protein in the cerebrospinal fluid in individuals with HD. […] The production of this toxic mutant huntingtin protein leads to progressive neuronal degeneration, ultimately leading to neuronal cell death.5 Levels of mHTT protein in cerebrospinal fluid have been shown to correlate with disease stage, symptom severity and markers of neuronal damage in people with HD.5 […] Researchers identified that the number of CAG trinucleotide repeat expansions in the huntingtin gene (HTT) has been shown to correlate with the age of disease onset.2,3 It is known that a CAG repeat length of 40 results in definite HD,1,7-10 CAG repeat length inversely correlates with age of onset,3,7 and other genetic and environmental factors may also affect disease progression.3,11

• #85 Surprise finding sheds light on what causes Huntington’s disease, a devastating fatal brain disorder | AP News

  https://apnews.com/article/huntingtons-disease-harvard-mit-genetic-involuntary-movement-b87b387b4ea37e41b43f4f9952b89117

  Scientists are unraveling the mystery of what triggers Huntingtons disease, a devastating and fatal hereditary disorder that strikes in the prime of life, causing nerve cells in parts of the brain to break down and die. […] The genetic mutation linked to Huntingtons has long been known, but scientists havent understood how people could have the mutation from birth, but not develop any problems until later in life. […] New research shows that the mutation is, surprisingly, harmless for decades. But it quietly grows into a larger mutation until it eventually crosses a threshold, generates toxic proteins, and kills the cells it has expanded in. […] They focused on the Huntingtons mutation, which involves a stretch of DNA in a particular gene where a three-letter sequence CAG is repeated at least 40 times. In people without the disease this sequence is repeated just 15 to 35 times. They discovered that DNA tracts with 40 or more such repeats expand over time until they are hundreds of CAGs long. Once CAGs reach a threshold of about 150, certain types of neurons sicken and die.

• #86 Surprising way that genetic mutation causes Huntington’s disease changes understanding of the disorder

  https://medicalxpress.com/news/2025-01-genetic-mutation-huntington-disease-disorder.html

  Scientists at the Broad Institute of MIT and Harvard, Harvard Medical School, and McLean Hospital have discovered a surprising mechanism by which the inherited genetic mutation known to cause Huntington’s disease leads to the death of brain cells. […] For 30 years, researchers have known that Huntington’s is caused by an inherited mutation in the Huntingtin (HTT) gene, but they didn’t know how the mutation causes brain cell death. […] A study published in Cell reveals that the inherited mutation doesn’t itself harm cells. Rather, the mutation is innocuous for decades but slowly morphs into a highly toxic form that then quickly kills the cell. […] The Huntington’s mutation involves a stretch of DNA in the HTT gene in which a three-letter sequence of DNA, „CAG,” is repeated at least 40 times, as opposed to the 15-35 repeats inherited by people without the disease.

• #87 Huntington’s disease | UK DRI

  https://www.ukdri.ac.uk/conditions/huntingtons-disease

  Prof Vincent Dion is harnessing CRISPR technology to edit genes directly and has shown in exciting proof-of-concept studies that he is able to ‘contract’ the expanded CAG repeat region in Huntington’s which could slow the progression of Huntington’s disease. […] Another promising area of research for Huntington’s disease relates to mechanisms of DNA repair which are thought to go wrong in the condition.

• #88 Surprising way that genetic mutation causes Huntington’s disease changes understanding of the disorder

  https://medicalxpress.com/news/2025-01-genetic-mutation-huntington-disease-disorder.html

  This type of „somatic expansion” occurs in only the specific types of brain cells that later die in Huntington’s disease. Only once a cell’s DNA expansion reaches a threshold number of CAGs—roughly 150—does the cell sicken and then die. The cumulative death of many such cells leads to the symptoms of Huntington’s disease. […] The study offers a potential explanation as to why candidate Huntington’s drugs that aim to reduce expression of the HTT protein have struggled in clinical trials: Very few cells have the toxic version of the protein at any given time, so the treatments may not be having a therapeutic effect in most cells. […] McCarroll’s team suggests that rather than targeting the HTT protein, a complementary or potentially better therapeutic approach could be to slow or stop the DNA-repeat expansion, which could help delay or even prevent the disease. […] More than 50 human brain disorders, including fragile X syndrome and myotonic dystrophy, are caused by expansions of DNA repeats in various genes.

Zobacz więcej