Cytosine-adenine-guaninePhenotypeGeneticHuntingtin proteinCausativeHuntington'sMutationProgressionNeurodegenerative diseaseOnsetNeuronsFMR1SymptomsAbnormalitiesAllelesHereditaryAlzheimer's DiseaseApproachesClinicalSCA3DementiaTypicallyAutophagyHuntington DiseaseFragileDeletionsTherapiesSpinocerebellarProgressesAdditionallyVariantsLargeDisordersAffectsStagesLiverDurationDevelopmentEarlierMovementsIncludeExpressionLeadsRegionFeatures
Cytosine-adenine-guanine4
- 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. (wikipedia.org)
- 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)
- 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)
Phenotype1
- In 1991, an international team of scientists, led by Dr. Warren, discovered the FMR1 gene and the mechanisms of trinucleotide repeat expansion that caused the fragile X phenotype. (emory.edu)
Genetic12
- The huntingtin gene provides the genetic information for huntingtin protein (Htt). (wikipedia.org)
- The genetic basis was discovered in 1993 by an international collaborative effort led by the Hereditary Disease Foundation. (wikipedia.org)
- Asymptomatic individuals should be tested for Huntington disease (HD) only if they have a family history of the disease, and only after genetic counseling. (arupconsult.com)
- Diagnostic genetic testing is indicated for individuals with or without a family history of HD after the onset of motor symptoms, particularly those severe enough to receive a score of 4 on the Unified Huntington's Disease Rating Scale (UHDRS) . (arupconsult.com)
- Predictive genetic testing may be indicated for asymptomatic individuals with a family history of the disease. (arupconsult.com)
- Longer repeats tend to be associated with earlier onset and more rapid progression, but there are many exceptions as well, likely due to genetic modifiers and other factors. (hopkinsguides.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)
- The differential diagnosis for the patient may include both genetic and non-genetic possibilities (for example, ataxia, dementia, and Parkinson disease). (medlink.com)
- Resistance to protein aggregation and the ability to restrict its associated cellular dysfunction are independently controlled by the natural variation in genetic background, revealing important new considerations in the search for targets for therapeutic intervention in conformational diseases. (biomedcentral.com)
- Yet age of onset can vary by several decades in people carrying the same length polyglutamine expansion, and a large proportion of this residual variation is genetic in nature and may be due to polymorphisms in other genes [ 12 - 15 ]. (biomedcentral.com)
- Much of the current knowledge about modifiers of conformational diseases has been gathered from linkage/association studies, candidate approaches, and unbiased genetic screens. (biomedcentral.com)
- Although genetic variants identified in this way are enormously informative about pathways that affect disease processes and that can, when perturbed, modify disease phenotypes [ 25 - 30 ], they are likely to be different from the naturally occurring variations. (biomedcentral.com)
Huntingtin protein2
- HD is caused by a CAG expansion mutation in the huntingtin (HTT) gene that affects the N-terminal polyglutamine of the encoded huntingtin protein. (hopkinsguides.com)
- For example in HD, the age of neurological onset is strongly associated with the length of polyglutamine (polyQ) expansion in huntingtin protein. (biomedcentral.com)
Causative2
- Dr. Warren used the unusual fragility of the X chromosome in patients with fragile X as a tool to begin the search for the causative gene, a tool that he shared with the other top scientists in the fragile X field. (emory.edu)
- Although these mutations themselves are causative, many disease characteristics such as age of onset, penetrance, and severity of specific symptoms can vary widely between individuals. (biomedcentral.com)
Huntington's5
- Huntington's disease (HD), also known as Huntington's chorea, is an incurable neurodegenerative disease that is mostly inherited. (wikipedia.org)
- Signs and symptoms of Huntington's disease most commonly become noticeable between the ages of 30 and 50 years, but they can begin at any age and present as a triad of motor, cognitive, and psychiatric symptoms. (wikipedia.org)
- When developed in an early stage, it is known as juvenile Huntington's disease. (wikipedia.org)
- [10] It has already described abnormalities in Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and multiple sclerosis among others. (aao.org)
- Monogenic gain-of-function protein aggregation diseases, including Huntington's disease, exhibit substantial variability in age of onset, penetrance, and clinical symptoms, even between individuals with similar or identical mutations. (biomedcentral.com)
Mutation1
- HD is typically inherited from an affected parent, who carries a mutation in the huntingtin gene (HTT). (wikipedia.org)
Progression4
- Research directions include determining the exact mechanism of the disease, improving animal models to aid with research, testing of medications and their delivery to treat symptoms or slow the progression of the disease, and studying procedures such as stem-cell therapy with the goal of replacing damaged or lost neurons. (wikipedia.org)
- Because of these advantages, OCT is now being explored as a potential tool to identify retinal changes in patients early in the course of NDDs, and to allow quantifiable, objective monitoring of axonal and neuronal loss with disease progression. (aao.org)
- The length of the CAG repeat explains 50-70% of the variance in age of onset and the rate of disease progression. (hopkinsguides.com)
- [ 2 ] All dementia share common molecular mechanisms responsible for disease etiology and progression, such as hypoxia and oxidative stress, neuroinflammation, mitochondrial bioenergetics, neurodegeneration, and blood-brain barrier permeability. (medscape.com)
Neurodegenerative disease1
- Alzheimer disease (AD) is the most common neurodegenerative disease responsible for dementia. (medscape.com)
Onset3
- A higher number of CAG repeats is associated with an earlier age of onset. (arupconsult.com)
- The number of repeats determines the risk and likely age of onset for symptom development. (arupconsult.com)
- This group of diseases is also characterized by an insidious onset in which neuropathological changes develop years before clinical presentation. (aao.org)
Neurons1
- To better understand the consequences of the absence of FMRP, we analyzed gene expression profiles and activities of cortical neural progenitor cells (NPCs) and neurons obtained from FXS patients' induced pluripotent stem cells (IPSCs) and IPSC-derived cells from FMR1 knock-out engineered using CRISPR-CAS9 technology. (bvsalud.org)
FMR13
- BACKGROUND: Fragile X syndrome (FXS) is a leading cause of autism spectrum disorder (ASD) and resulted from a loss of the FMR1-encoded fragile X messenger ribonucleoprotein 1 (FMRP) protein due to large CGG repeat expansions in the promoter region of the FMR1 gene. (bvsalud.org)
- The microtubule-associated protein Tau is a promising target for Tauopathic diseases and our preliminary study found that Tau protein levels were increased in the brain of Fmr1 knockout (KO) mice, a model of FXS. (bvsalud.org)
- Fragile X syndrome (FXS) is caused by a repression of the FMR1 gene that codes the Fragile X mental retardation protein (FMRP), an RNA binding protein involved in processes that are crucial for proper brain development. (bvsalud.org)
Symptoms3
- About eight percent of cases start before the age of 20 years, and are known as juvenile HD, which typically present with the slow movement symptoms of Parkinson's disease rather than those of chorea. (wikipedia.org)
- Although there is no known cure for HD, a diagnosis may enable treatment of some of the physical and psychiatric symptoms, which can be managed with pharmacologic therapy in the earlier stages of the disease. (arupconsult.com)
- The presenting signs and symptoms in patients with ATTR are fairly nonspecific and are often attributed to more common diseases affecting both the heart and the peripheral nervous system (PNS) and autonomic nervous system. (medscape.com)
Abnormalities1
- Huntington disease (HD) is a progressive, hereditary, neurodegenerative disorder that is characterized by abnormalities in motor skills, cognitive skills, and psychiatric changes. (arupconsult.com)
Alleles2
- Those with intermediate alleles are prone to this repeat instability and may have children with an HD-causing allele. (arupconsult.com)
- One individual was found to carry a 12 kb deletion in one copy of the ASPA gene on 17p13, which when mutated in both alleles leads to Canavan disease. (biomedcentral.com)
Hereditary3
- However, how lncRNAs contribute to the development of hereditary diseases in human is still mostly unknown. (biomedcentral.com)
- This review is focused on hereditary diseases in the pathogenesis of which long non-coding RNAs play an important role. (biomedcentral.com)
- Future research will help translate this knowledge into clinical practice which will not only lead to an increase in the diagnostic rate but also in the future can help with the development of etiotropic treatments for hereditary diseases. (biomedcentral.com)
Alzheimer's Disease1
Approaches2
- New approaches for staging HD based on CAG repeat length as well as emerging biomarker data have been proposed but are not in use yet [2] . (hopkinsguides.com)
- First, these approaches are designed to identify individual modifier genes with strong phenotypic effects. (biomedcentral.com)
Clinical1
SCA31
- Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is characterized by progressive cerebellar ataxia and variable findings including pyramidal signs, a dystonic-rigid extrapyramidal syndrome, significant peripheral amyotrophy and generalized areflexia, progressive external ophthalmoplegia, action-induced facial and lingual fasciculations, and bulging eyes. (nih.gov)
Dementia2
- Multiple neuropathologic processes may underlie dementia , including both neurodegenerative diseases and vascular disease. (medscape.com)
- Furthermore, comorbidity (the presence of more than one disease process) is the rule rather than the exception for dementia in elderly persons. (medscape.com)
Typically1
- Death typically occurs 15-20 years from when the disease was first detected. (wikipedia.org)
Autophagy1
- Similarly, gene set analysis evidenced a significant downregulation in gene ontology terms related to autophagy in FXTAS samples. (bvsalud.org)
Huntington Disease8
- What causes Huntington disease? (arupconsult.com)
- Can someone develop Huntington disease without a family history? (arupconsult.com)
- Should asymptomatic individuals be tested for Huntington disease? (arupconsult.com)
- Caron NS, Wright GEB, Hayden MR. Huntington disease . (arupconsult.com)
- Huntington disease (HD) is a neurodegenerative trinucleotide repeat disorder characterized by progressive motor and cognitive dysfunction, as well as psychiatric disorders. (hopkinsguides.com)
- Cognitive impairment due to Huntington disease is classified under the neurocognitive disorders (NCDs) section of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) [8] . (hopkinsguides.com)
- Johns Hopkins Guides , www.hopkinsguides.com/hopkins/view/Johns_Hopkins_Psychiatry_Guide/787115/0/Huntington_Disease. (hopkinsguides.com)
- J, Bang J, Ross CA. Huntington Disease. (hopkinsguides.com)
Fragile1
- Since FXS cannot always be identified by cytogenetic analysis, molecular testing of the fragile X mental retardation 1 CGG repeat was performed in 440 samples. (wjgnet.com)
Deletions1
- Whole exome sequencing is not suitable for detecting polynucleotide repeat disorders or large insertion/deletions. (medlink.com)
Therapies1
- It is a fatal disorder for which there are no disease-modifying therapies, though symptomatic treatments are available. (hopkinsguides.com)
Spinocerebellar2
- This test is not a gene panel for all types of spinocerebellar ataxia (SCA). (mayocliniclabs.com)
- order SCAP / Spinocerebellar Ataxia Repeat Expansion Panel, Varies. (mayocliniclabs.com)
Progresses1
- Pathologically, HD causes selective degeneration of the striatum (especially caudate), though many other regions subsequently atrophy as the disease progresses. (hopkinsguides.com)
Additionally1
- Additionally, testing for ATXN1 assesses for CAT ( cytosine-adenine-thymine ) trinucleotides that interrupt the CAG repeat tract. (mayocliniclabs.com)
Variants1
- Two subjects showed partial duplication of the TM4SF2 gene on Xp11.4, previously implicated in X-linked non-specific mental retardation, but in our subsequent analyses such variants were also found in controls. (biomedcentral.com)
Large2
- However, large expansions of the CAG repeat region can occur during sperm formation. (arupconsult.com)
- The results in PAR1/PAR2 are the first large-scale studies of gene dosage in these regions, and the findings at the ASMT locus indicate that further studies of the duplication of the ASMT gene are needed in order to gain insight into its potential involvement in ASD. (biomedcentral.com)
Disorders2
- Neurodegenerative diseases (NDDs) are devastating disorders which impair memory, cognition, movements, and general functioning. (aao.org)
- Next-generation sequencing of the whole exome is useful for testing for multiple candidate genes simultaneously or for discovering new, rare disorders. (medlink.com)
Affects1
- The disease affects men and women equally. (wikipedia.org)
Stages2
- No cure for HD is known, and full-time care is required in the later stages. (wikipedia.org)
- however, a variable but measurable amount of AD pathologic changes exist in most cognitively intact elderly individuals who undergo autopsy, indicating that AD is a chronic disease with latent and prodromal stages and suggesting that individuals may have varying abilities to compensate, either biologically or functionally, for the presence of AD. (medscape.com)
Liver2
Duration1
- However, the number of CAG repeats is not indicative of the duration of the illness or the rate of deterioration. (arupconsult.com)
Development1
- Several agents that seek to exert disease-modifying effects by lowering Htt levels-notably anti-sense oligonucleotide (ASO) formulations-are in development, but results so far have been disappointing [3] . (hopkinsguides.com)
Earlier1
- The disease may develop earlier in each successive generation. (wikipedia.org)
Movements1
- As the disease advances, uncoordinated, involuntary body movements of chorea become more apparent. (wikipedia.org)
Include1
- Genes in these two novel duplications include GABRB3 and ATP10A in one case, and MKRN3 , MAGEL2 and NDN in the other. (biomedcentral.com)
Expression1
- Numerous cellular proteins detect DNA damage and induce senescence , a permanent change of state characterized by morphological and gene expression changes. (massgenomics.org)
Leads1
- 39 leads to HD with full penetrance. (hopkinsguides.com)
Region1
- A partial duplication in the ASMT gene, located in the pseudoautosomal region 1 (PAR1) of the sex chromosomes and previously suggested to be involved in ASD susceptibility, was observed in 6-7% of the cases but in only 2% of controls (P = 0.003). (biomedcentral.com)
Features1
- The phenotypes were comparable up to a deletion size of 7.1 Mb, and most features could be attributed to the terminally located gene DLL1 . (biomedcentral.com)