Huntington Disease (HTT)
| Dred_ID | RD00009 |
| OMIM ID | 143100 |
| Disease name | Huntington Disease |
| Alternative names | HD Huntington Chorea |
| Category | Genetic diseases, Rare diseases, Neuronal diseases |
| Phenotype | NIH Rare Diseases: Huntington disease (HD) is an inherited condition that causes progressive degeneration of neurons in the brain. Signs and symptoms usually develop between ages 35 to 44 years and may include uncontrolled movements, loss of intellectual abilities, and various emotional and psychiatric problems. People with HD usually live for about 15 to 20 years after the condition begins. It is caused by changes (mutations) in the HTT gene and is inherited in an autosomal dominant manner. Treatment is based on the symptoms present in each person and may include various medications. There is also a less common, early-onset form of HD which begins in childhood or adolescence. For more information on this form, please visit GARD's juvenile Huntington disease Web page.
OMIM: Huntington disease (HD) is an autosomal dominant progressive neurodegenerative disorder with a distinct phenotype characterized by chorea, dystonia, incoordination, cognitive decline, and behavioral difficulties. There is progressive, selective neural cell loss and atrophy in the caudate and putamen. Walker (2007) provided a detailed review of Huntington disease, including clinical features, population genetics, molecular biology, and animal models. |
| Miscellaneouse | OMIM: onset first to seventh decade with 30 to 40 year mode prevalence much higher in whites than blacks juvenile rigid early-onset form more often paternally inherited normal range of expanded repeats 9-29, hd range 36-121 complete penetrance |
| Prevalence | Prevalence: 1-9/100000 (Europe) [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | HTT |
| Alias symbols | HD; IT15 |
| Gene name | huntingtin |
| Gene map locus | 4p16.3; chr4:3,041,363-3,243,960(+) |
| Ensembl Gene ID | ENSG00000197386 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | Huntingtin is a disease gene linked to Huntington's disease, a neurodegenerative disorder characterized by loss of striatal neurons. This is thought to be caused by an expanded, unstable trinucleotide repeat in the huntingtin gene, which translates as a polyglutamine repeat in the protein product. A fairly broad range of trinucleotide repeats (9-35) has been identified in normal controls, and repeat numbers in excess of 40 have been described as pathological. The huntingtin locus is large, spanning 180 kb and consisting of 67 exons. The huntingtin gene is widely expressed and is required for normal development. It is expressed as 2 alternatively polyadenylated forms displaying different relative abundance in various fetal and adult tissues. The larger transcript is approximately 13.7 kb and is expressed predominantly in adult and fetal brain whereas the smaller transcript of approximately 10.3 kb is more widely expressed. The genetic defect leading to Huntington's disease may not necessarily eliminate transcription, but may confer a new property on the mRNA or alter the function of the protein. One candidate is the huntingtin-associated protein-1, highly expressed in brain, which has increased affinity for huntingtin protein with expanded polyglutamine repeats. This gene contains an upstream open reading frame in the 5' UTR that inhibits expression of the huntingtin gene product through translational repression. [provided by RefSeq, Jul 2016] |
| Repeat unit | CAG |
| Normal repeat copies | 9-29 |
| Pathogenic repeat copies | ≥36 |
| Gene | HTT |
| Repeat location | CDS |
| Chromosome locus | chr4:3074877-3074942 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | protein |
| Possible toxicity | To understand how the presence of misfolded proteins leads to cellular dysfunction, Gidalevitz et al. (2006) employed C. elegans polyglutamine aggregation models and found that polyglutamine expansions disrupted the global balance of protein folding quality control, resulting in loss of function of diverse metastable proteins with destabilizing temperature-sensitive mutations. In turn, these proteins, although innocuous under normal physiologic conditions, enhanced the aggregation of polyglutamine proteins. Thus, Gidalevitz et al. (2006) suggested that weak folding mutations throughout the genome can function as modifiers of polyglutamine phenotypes and toxicity. [By OMIM] |
| Pathway annotation | Reactome, KEGG |
| PMID | 15483602 |
| Authors | Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S |
| Title | Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death |
| Journal | Nature. 431(7010):805-10 |
| Year | 2004 |
| PMID | 19776381 |
| Authors | Aziz NA, Jurgens CK, Landwehrmeyer GB; EHDN Registry Study Group, van Roon-Mom WM, van Ommen GJ, Stijnen T, Roos RA |
| Title | Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease |
| Journal | Neurology. 73(16):1280-5 |
| Year | 2009 |