• Huntington's disease (HD) is an autosomal dominant neurodegenerative condition associated with abnormal movements, cognitive deterioration, and psychiatric symptoms. (bmj.com)
  • Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by a dynamic mutation due to the expansion of CAG repeats in the HTT gene (4p16.3). (geneticsmr.com)
  • Huntington disease (HD), an autosomal dominant, progressive neurodegenerative disorder, is caused by an expanded CAG repeat sequence leading to an increase in the number of glutamine residues in the encoded protein 1 . (nature.com)
  • As with many neurodegenerative diseases, both rare autosomal-dominant forms of AD and more common sporadic forms with genetic risk factors without causative mutations exist. (medscape.com)
  • Huntington's disease (HD) is the most prevalent autosomal dominant, trinucleotide repeat neurodegenerative disease. (grantome.com)
  • HD is an autosomal dominant inherited neurodegenerative disease that becomes manifest in midlife and causes progressive motor, psychiatric, and cognitive dysfunction. (jci.org)
  • Huntington's Disease (HD) is an autosomal dominant, progressive neurodegenerative disorder characterized by motor disturbance, cognitive loss, and psychiatric manifestations, which usually manifests at around 40 to 50 years of age. (upmc.com)
  • Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. (nature.com)
  • A fascinating example of enhanced cell-type-specific disease vulnerability is seen in Huntington's disease (HD), a monogenic neurodegenerative disease caused by expansion of CAG (glutamine-encoding) trinucleotide repeats in the huntingtin gene. (mit.edu)
  • The huntingtin gene encodes a protein of 350 kD;the disease causing mutation is an expansion of an amino-terminal polyglutamine repeat of more than 36 successive glutamines. (grantome.com)
  • METHODS We cotransfected neuronal (SK-N-SH, human neuroblastoma) and non-neuronal (COS-7, monkey kidney) cell lines with HD exon 1 (containing either 21 or 72 CAG repeats) construct DNA and either full length wild type huntingtin or pFLAG (control vector). (bmj.com)
  • RESULTS Full length wild type huntingtin significantly reduced cell death resulting from the mutant HD exon 1 fragments containing 72 CAG repeats in both cell lines. (bmj.com)
  • Wild type huntingtin did not significantly modulate cell death caused by transfection of HD exon 1 fragments containing 21 CAG repeats in either cell line. (bmj.com)
  • This stretch is encoded by a trinucleotide CAG repetition in exon 1 of HTT. (altmetric.com)
  • Exon 1 contains a CAG trinucleotide repeat that encodes the amino acid glutamine, followed by another repeat that encodes proline. (jci.org)
  • trinucleotides or hexanucleotides), alterations in most regulatory regions (promoter regions) or deep intronic regions (greater than 20bp from an exon). (tesiscolorado.com)
  • HTT is the gene implicated in HD and contains a normally polymorphic trinucleotide CAG repeat region in the first exon. (upmc.com)
  • Huntington disease (HD) is a neurodegenerative disorder caused by an unstable and progressive expansion of a CAG trinucleotide repeat tract in the HD gene. (nih.gov)
  • Huntington's disease is a genetic neurological disorder caused by a repeated expansion of the CAG trinucleotide, causing instability in the N-terminal of the gene coding for the Huntingtin protein. (benthamscience.com)
  • Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a trinucleotide repeat expansion in the gene coding for huntingtin (mHTT). (mdsabstracts.org)
  • Huntington's disease (HD) is a neurodegenerative disorder caused by a dominantly heritable expansion of a trinucleotide CAG repeat in the huntingtin (htt) gene [ 15 ], and characterized by the preferential neurodegeneration of striatal medium-sized spiny neurons [ 16 ]. (biomedcentral.com)
  • Huntington's disease (HD) is a neurodegenerative disorder caused by an unstable CAG repeat. (torvergata.it)
  • Huntington's disease is a neurodegenerative disorder caused by a mutation on the HD gene, producing a polyglutamin (polyQ) expansion on the N-terminus of Htt. (novusbio.com)
  • The spinocerebellar ataxias (SCAs) are dominantly inherited neurodegenerative disorders characterized by a progressive loss of balance and coordination, and eventually the inability to coordinate swallowing and breathing. (bcm.edu)
  • Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder with 100% penetrance. (sketchy.com)
  • CAG repeats that exceed thirty-five can cause a gain-of-function mutation in ATN1. (wikipedia.org)
  • The knock-in mice carrying a 72-80 CAG repeat mutation is an accurate genetic model of early stage HD, displaying a more subtle disease phenotype. (nih.gov)
  • The causative mutation is a (CAG) n trinucleotide repeat expansion of more than 35 repeats, which is translated into an abnormally long polyglutamine tract in the huntingtin protein. (bmj.com)
  • 2 The polyglutamine expansion mutation causes disease by conferring a novel deleterious function on the mutant protein and the severity correlates with increasing CAG repeat number and expression levels in transgenic mice and in cell culture models. (bmj.com)
  • In collaboration with Harry Orr's group (University of Minnesota), we determined that the mutation responsible for SCA1 is an expansion of a CAG trinucleotide repeat encoding glutamine in the protein Ataxin-1. (bcm.edu)
  • For instance, if you've got a mutation caused by triplet repeat expansion, for instance in the Huntington's gene, where the trinucleotide repeats a CAG, you might have 17 CAGs in a normal chromosome. (hstalks.com)
  • The mutation leads to the abnormal expansion of the production of the polyglutamine tract (polyQ) resulting in the form of an unstable Huntingtin protein commonly referred to as mutant Huntingtin. (benthamscience.com)
  • The mutation associated with clinical manifestations of HD is a CAG trinucleotide repeat expansion in the HD gene (3). (torvergata.it)
  • Instability of highly expanded CAG repeats in mice transgenic for the Huntington's disease mutation. (nature.com)
  • Expansions of certain trinucleotide repeats cause neurodegenerative disorders of which Huntington's disease constitutes the most common example. (uni-muenchen.de)
  • Here, we test the hypothesis that variation within the IT15 gene on chromosome 4, whose expansion causes Huntington's disease, influences normal human brain structure. (uni-muenchen.de)
  • We found an increase of GM with increasing long CAG repeat and its interaction with age within the pallidum, which is involved in Huntington's disease. (uni-muenchen.de)
  • HD also displays anticipation , a phenomenon where subsequent generations manifest the disease at an earlier age and with increased severity due to the expansion of the trinucleotide repeat. (sketchy.com)
  • Notably, paternal inheritance usually results in more severe disease outcomes due to higher CAG expansion during spermatogenesis. (sketchy.com)
  • Parkinson's Disease is a neurodegenerative disorder primarily characterized by bradykinesia, or slowed movement. (sketchy.com)
  • Recent evidence suggests that PTSD may be a risk factor for the development of subsequent neurodegenerative disorders, including Alzheimer's dementia and Parkinson's disease. (preprints.org)
  • These results provide a mechanistic basis for the role of FAN1 in preventing repeat expansion and could explain the antagonistic effects of MMR and FAN1 in disease onset/progression. (bvsalud.org)
  • Huntington's disease (HD) is a neurodegenerative disorder characterized by a triad of choreoathetosis, dementia and dominant inheritance. (e-jmd.org)
  • Late-onset (≥ 60 years) HD is clinically different from other adult or juvenile onset HD and characterized by mild motor problem as the initial symptoms, shorter disease duration, frequent lack of family history, and relatively low CAG repeats expansion. (e-jmd.org)
  • Innate immunity is central to the pathophysiology of neurodegenerative disorders, but it remains unclear why immunity is altered in the disease state and whether changes in immunity are a cause or a consequence of neuronal dysfunction. (shengsci.com)
  • Neuropathological diagnosis and CAG repeat expansion in Huntington's disease. (mdsabstracts.org)
  • However, the role of Rsk in this neurodegenerative disease remains unknown. (biomedcentral.com)
  • Using the largest cohort of HD patients analyzed to date (2913 individuals from 40 centers worldwide), we developed a parametric survival model based on CAG repeat length to predict the probability of neurological disease onset (based on motor neurological symptoms rather than psychiatric onset) at different ages for individual patients. (torvergata.it)
  • Huntington's disease (HD, MIM 143100) is a progressive, neurodegenerative disorder that presents with motor disturbances, psychiatric symptoms, and cognitive decline. (torvergata.it)
  • When translated into protein the CAG repeat encodes for a polyglutamine stretch in the disease-causing proteins. (biologie-uni-siegen.de)
  • Objective: Polyglutamine proteins can cause a wide range of neurodegenerative disorders upon long-range expansions such as Huntington's disease and spinocerebellar ataxia (SCA). (videolectures.net)
  • Involvement of other CAG-repeat genes has only been moderately investigated or reported, although an association was found with intermediate length in the ATXN1 in a small Italian cohort after discovery of a pedigree with co-occurrence of ALS and SCA1 disease. (videolectures.net)
  • Approximately 55 percent were felt to have a single progressive neurodegenerative etiology, predominantly Alzheimer disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), dementia related to Parkinson disease (PD), and corticobasal degeneration (including corticobasal syndrome and many other phenotypes) [ 2 ]. (medilib.ir)
  • A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. (nature.com)
  • Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15. (nature.com)
  • Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. (nature.com)
  • Trottier, Y., Biancalana, V. & Mandel, J.L. Instability of CAG repeats in Huntington's disease: relation to parental transmission and age of onset. (nature.com)
  • Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. (nature.com)
  • Huntington disease (HD) is a progressive, hereditary, neurodegenerative disorder that is characterized by abnormalities in motor skills, cognitive skills, and psychiatric changes. (arupconsult.com)
  • Huntington disease (HD) is caused by an expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats within the HTT gene. (arupconsult.com)
  • Individuals with intermediate alleles (27-35 cytosine-adenine-guanine [CAG] repeats) typically do not have symptoms of Huntington disease (HD). (arupconsult.com)
  • Alzheimer disease (AD) is the most common neurodegenerative disease responsible for dementia. (medscape.com)
  • Huntington's disease (HD) is a progressive neurodegenerative illness that affects 2-9/100.000 of the general population. (altmetric.com)
  • The number of repeats is inversely correlated with the age of onset of motor symptoms, and disease onset during childhood or adolescence is associated with more than 60 CAG repeats. (altmetric.com)
  • Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes. (cdc.gov)
  • Parkinson's disease and Huntington's disease both involve the central nervous system and are neurodegenerative, which means they cause the gradual death of nerve cells. (medicalnewstoday.com)
  • The higher the number of CAG repeats, the earlier the age of onset and the greater the severity of the disease. (medicalnewstoday.com)
  • Huntingtin Antibody was prepared from whole rabbit serum produced by repeated immunizations with a synthetic peptide corresponding to the C-terminus of human Huntingtin disease protein. (novusbio.com)
  • The age of onset of the disease varies inversely with the number of CAG repeats. (jci.org)
  • The Parkinson's Disease Comprehensive Panel examines 26 genes associated with an increased risk of developing the neurodegenerative condition Parkinson's Disease. (tesiscolorado.com)
  • The Alzheimer-Dementia Panel examines 16 genes associated with an increased risk of developing neurodegenerative conditions: Alzheimer's disease and genetic disorders that cause dementia. (tesiscolorado.com)
  • Patients identified with a disease-causing change (a pathogenic or likely pathogenic variant) in a gene on this panel have an increased risk of developing the associated neurodegenerative disease. (tesiscolorado.com)
  • This assay will not detect certain types of genomic alterations which may cause disease such as, but not limited to, translocations or inversions, repeat expansions (eg. (tesiscolorado.com)
  • The penetrance of the CAG expansion is not complete, therefore showing variability in the severity of disease symptoms. (upmc.com)
  • Individuals with a CAG repeat size of 30 to 35 do not manifest Huntington's Disease themselves, however, the risk that their offspring will develop HD may be increased, particularly from paternal transmission of the gene. (upmc.com)
  • Detection of CAG expansions in the HTT gene that lead to Huntington's Disease. (upmc.com)
  • Huntington's disease (HD) is one of the most common tandem repeat disorders and presents as a unique trilogy of cognitive, psychiatric and motor symptoms. (biomedcentral.com)
  • Huntington's disease (HD), which presents with a wide range of neurological, psychiatric and other symptoms [ 1 ], is one of the most common and is caused by a tandem repeat (CAG) expansion leading to an expanded polyglutamine tract in the disease protein (huntingtin). (biomedcentral.com)
  • Andrew, S.E., Goldberg, Y.P. & Hayden, M.R. Rethinking genotype and phenotype correlations in polyglutamine expansion disorders. (nature.com)
  • Polymerase chain reaction (PCR) testing and size analysis for an expanded number of cytosine-adenine-guanine (CAG) trinucleotide repeats in the HTT gene may be performed for both symptomatic individuals and asymptomatic individuals with a family history of HD. (arupconsult.com)
  • The expansion of the cytosine-adenine-guanine (CAG) trinucleotide in the HTT gene leads to the production of atypical protein. (medicalnewstoday.com)
  • The encoded protein includes a serine repeat and a region of alternating acidic and basic amino acids, as well as the variable glutamine repeat. (wikipedia.org)
  • In addition to encoding neurotoxic protein species, the CAG repeat RNA can have a toxic function itself. (biologie-uni-siegen.de)
  • For example, we have identified a protein complex, which binds to and induces aberrant translation of mRNAs containing mutant CAG repeats. (biologie-uni-siegen.de)
  • With increasing repeat number, the protein changes conformation and becomes increasingly prone to aggregation 11 , suggesting important functional correlations between repeat length and pathology. (nature.com)
  • Lately, in 1993, gene IT15 (interesting transcript 15), which codes unstable protein huntingtin (htt) comprising variable number of CAG repeats, was identified [ 5 ]. (hindawi.com)
  • ataxias Spinocerebellar ataxias (SCAs) represent several intensifying hereditary neurodegenerative illnesses that change from one another in clinical demonstration and hereditary basis. (ampkpathway.com)
  • Spinocerebellar ataxia type 1 is caused by expansion of a translated CAG repeat in ataxin1 (ATXN1). (nih.gov)
  • Co-transcriptional formation of stable RNA·DNA hybrids can also enhance the instability of repeat tracts. (bvsalud.org)
  • Our results show that Msh2 is required for somatic instability of the CAG repeat. (nature.com)
  • Figure 3: Levels of CAG repeat instability in various tissues from Msh2 -/- , Msh2 +/- and Msh2 +/+ mice. (nature.com)
  • Those with intermediate alleles are prone to this repeat instability and may have children with an HD-causing allele. (arupconsult.com)
  • In 278 normal subjects, we determined CAG repeat length within the IT15 gene on chromosome 4 and analyzed high-resolution T1-weighted magnetic resonance images by the use of voxel-based morphometry. (uni-muenchen.de)
  • But in a diseased chromosome, you might have 40 successive copies of CAG trinucleotides in the gene. (hstalks.com)
  • HD arises from a CAG trinucleotide repeat expansion on chromosome 4 . (sketchy.com)
  • Preventing polyglutamine repeat oligomerization reverses symptoms of Huntington's chorea. (the-scientist.com)
  • To relate full-length HD gene expression and differential polyglutamine expansion with possible pathophysiological changes in salient electrophysiological properties of neurons that may underlie early symptoms of HD, including mood and cognitive impairments, we have conducted whole-cell recordings from hippocampal area CA1 pyramidal cells in Hdh6/Q72 and Hdh4/Q80 knock-in mice. (nih.gov)
  • motor symptoms (chorea, ataxia) at age 36 and was diagnosed with HD with 60 CAG repeats. (mdsabstracts.org)
  • Persons affected with HD have a CAG repeat length (CAG) between 36 and 250, though some individuals with a CAG less than 42 will never show symptoms (4-8). (torvergata.it)
  • In all cases, age at onset correlates inversely with repeat number. (bmj.com)
  • OBJECTIVES Recent data suggest that wild type huntingtin can protect against apoptosis in the testis of mice expressing full length huntingtin transgenes with expanded CAG repeats. (bmj.com)
  • We were interested to test if wild type huntingtin protected against the toxicity of polyglutamine expansion mutations. (bmj.com)
  • The decision to rescreen a patient should be undertaken only with the guidance of a genetics professional who can best assess the incremental benefit of repeat testing for additional mutations. (acog.org)
  • Polyglutamine expansion =} Huntington accumulates in nucleus and cytoplasm =} cytoplasmic Huntington aggregates in axonal terminals, neuronal loss and gliosis. (neuroradiologycases.com)
  • Our study demonstrates that a certain trinucleotide repeat influences normal brain structure in humans. (uni-muenchen.de)
  • Interestingly, in contrast to ATXN2, we found a relative high frequency of intermediate expansions in ATXN1 in both ALS (1-2% in ATXN2 vs 6-7% in ATXN1) and control individuals (0.3-0.4% in ATXN2 vs 5-6% in ATXN1). (videolectures.net)
  • Intermediate alleles (IAs) show 27 to 35 CAG repeats and expanded alleles have more than 35 repeats. (geneticsmr.com)
  • Intermediate length of the polyglutamine coding CAG/CAA trinucleotide repeat in the ATXN2 gene was shown to be a risk factor for amyotrophic lateral sclerosis (ALS). (videolectures.net)
  • After identification of a similar pedigree, we set out to investigate the frequency of ATXN1 intermediate expansions in a large international cohort of ALS patients and controls. (videolectures.net)
  • An intermediate cut-off was determined via control distribution and was found to be at 33 CAG/CAT repeats and higher. (videolectures.net)
  • Results: We found 242 (11.4%) intermediate expansion carriers in control individuals and 333 (13.8%) in ALS patients. (videolectures.net)
  • This fits with the hypothesis that intermediate polyglutamine expansions might not be causative but pose an increased risk for developing ALS. (videolectures.net)
  • However, large expansions of the CAG repeat region can occur during sperm formation. (arupconsult.com)
  • Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder characterized by cerebellar ataxia, myoclonic epilepsy, choreoathetosis, and dementia. (wikipedia.org)
  • Several such studies have indicated that such medications may produce modest improvement in ataxia caused by various neurodegenerative conditions, including OPCA. (medscape.com)
  • Myotonic dystrophy type 1 is the most frequent form of muscular dystrophy in adults caused by an abnormal expansion of the CTG trinucleotide. (bvsalud.org)
  • Structurally, mutant CAG repeat RNA differs from the physiological RNA: the expanded CAG repeats fold into characteristic hairpin structures. (biologie-uni-siegen.de)
  • Mutant form of huntingtin (mhtt) comprises up to 40 repeats and individuals with 36-39 CAG repeats are in risk of developing adult (late-onset) form of HD. (hindawi.com)
  • Such molecular defect is based on the expansion of this triplet that codes amino acid glutamine. (hindawi.com)
  • We provide estimated probabilities of onset associated with CAG repeats between 36 and 56 for individuals of any age with narrow confidence intervals. (torvergata.it)
  • In unaffected individuals, there are 10-34 CAG repeats. (jci.org)
  • Individuals with juvenile onset usually have over 55 repeats, and they usually inherit the gene from their father. (jci.org)
  • Normal individuals have between 6 and 35 copies of this repeat. (upmc.com)
  • Affected individuals have an expanded repeat region, usually 36 to 121 copies of the repeat. (upmc.com)
  • To understand the molecular basis of these opposing effects, we evaluated FAN1 nuclease function on DNA extrahelical extrusions that represent key intermediates in triplet repeat expansion. (bvsalud.org)
  • Activation of FAN1 in this manner results in DNA cleavage in the vicinity of triplet repeat extrahelical extrusions thereby leading to their removal in human cell extracts. (bvsalud.org)
  • 4 months) HD mice harbouring an expanded CAG repeat stretch and age-matched wild type (WT) mice revealed no significant differences in any of the active or passive membrane properties investigated. (nih.gov)
  • This enables us to follow histopathological changes in course of neurodegenerative process (NDP) within the striatum and compare them with postmortem samples of human HD brains. (hindawi.com)
  • 18 months) HD mice and WT controls, despite modest levels of repeat length variability demonstrated by single cell PCR. (nih.gov)
  • Figure 1: Typical GeneScan traces for sizing of the CAG repeat from heart and striatal tissue of Msh2 -/- and Msh2 +/+ mice. (nature.com)
  • Figure 2: Distribution of CAG repeats before and after the major GeneScan peak for various tissues from Msh2 -/- and Msh2 +/+ mice. (nature.com)
  • Identification of biomarkers known to be associated with neurodegeneration in patients with PTSD would shed light on the pathophysiological mechanisms linking these disorders, and would also help in the development of preventive approaches aimed at reducing the risk of neurodegenerative disorders in PTSD. (preprints.org)