Dentatorubral-Pallidoluysian Atrophy, Naito-Oyanagi Disease (ATN1)
| Dred_ID | RD00008 |
| OMIM ID | 125370 |
| Disease name | Dentatorubral-Pallidoluysian Atrophy, Naito-Oyanagi Disease |
| Alternative names | Naito-Oyanagi Disease DRPLA |
| Category | Genetic diseases, Rare diseases, Neuronal diseases, Mental diseases |
| Phenotype | NIH Rare Diseases: Dentatorubral-pallidoluysian atrophy (DRPLA) is a brain disorder that worsens over time. It can lead to involuntary movements, mental and emotional problems, and a decline in thinking ability. Symptoms usually appear around 30 years of age, but can occur anytime from infancy to mid-adulthood. Specific signs and symptoms may differ and include seizures, issues with balance and coordination (ataxia), and involuntary muscle jerking or twitching (myoclonus). Other symptoms that usually appear in adulthood include dementia and psychiatric conditions. DRPLA is caused by a mutation in the ATN1 gene and is inherited in an autosomal dominant manner. Although there is no specific treatment or cure for DRPLA, there may be ways to manage the symptoms. A team of doctors is often needed to figure out the treatment options based on each person’s symptoms.
OMIM: Naito and Oyanagi (1982) reported a syndrome of myoclonic epilepsy, dementia, ataxia, and choreoathetosis. At autopsy, major neuropathologic changes consisted of combined degeneration of the dentatorubral and pallidoluysian systems. Inheritance was autosomal dominant. Onset was usually in the twenties and death in the forties. Although this condition was perhaps first described by Smith et al. (1958) and several sporadic cases have been reported from Western countries, this disorder seems to be very rare except in Japan where other hereditary cases have been described (Iizuka et al., 1984; Iwabuchi et al., 1985; Takahashi et al., 1988). Hirayama et al. (1981) classified 3 clinical forms of DRPLA: the ataxo-choreoathetoid form, the pseudo-Huntington form, and the myoclonic epilepsy form. |
| Miscellaneouse | OMIM: genetic anticipation mean age of onset 30 years (range first to seventh decade) phenotypic heterogeneity |
| Prevalence | Prevalence: 1-9/1000000 (Japan) [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | ATN1 |
| Alias symbols | B37; HRS; NOD; DRPLA; D12S755E |
| Gene name | atrophin 1 |
| Gene map locus | 12p13.31; chr12:6,924,459-6,942,321(+) |
| Ensembl Gene ID | ENSG00000111676 |
| 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 | Dentatorubral pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder characterized by cerebellar ataxia, myoclonic epilepsy, choreoathetosis, and dementia. The disorder is related to the expansion from 7-35 copies to 49-93 copies of a trinucleotide repeat (CAG/CAA) within this gene. The encoded protein includes a serine repeat and a region of alternating acidic and basic amino acids, as well as the variable glutamine repeat. Alternative splicing results in two transcripts variants that encode the same protein. [provided by RefSeq, Jul 2016] |
| Repeat unit | CAG |
| Normal repeat copies | 6-35 |
| Pathogenic repeat copies | ≥49 |
| Gene | ATN1 |
| Repeat location | CDS |
| Chromosome locus | chr12:6936717-6936776 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | Protein |
| Possible toxicity | Yamada et al. (2002) noted that some patients with DRPLA have white matter lesions characterized neuropathologically by diffuse myelin pallor. The number of lesions correlates with increasing age, being milder in degree in juveniles and more severe in older adults. In immunohistochemical studies of brains of 12 affected patients and transgenic mice with expanded (CAG)n repeats, Yamada et al. (2002) found immunoreactivity for polyQ in some glial nuclei that was increased with larger expansions of (CAG)n repeats. The authors concluded that oligodendrocytes are a target for the polyQ pathogenesis in DRPLA and may lead to white matter degeneration. [By OMIM] |
| Pathway annotation | Reactome, KEGG |
| PMID | 23933208 |
| Authors | Suzuki Y, Jin C, Yazawa I |
| Title | Increased aggregation of polyleucine compared with that of polyglutamine in dentatorubral-pallidoluysian atrophy protein |
| Journal | Neurosci Lett. 552:156-61 |
| Year | 2013 |
| PMID | 22342974 |
| Authors | Suzuki K, Zhou J, Sato T, Takao K, Miyagawa T, Oyake M, Yamada M, Takahashi H, Takahashi Y, Goto J, Tsuji S |
| Title | DRPLA transgenic mouse substrains carrying single copy of full-length mutant human DRPLA gene with variable sizes of expanded CAG repeats exhibit CAG repeat length- and age-dependent changes in behavioral abnormalities and gene expression profiles |
| Journal | Neurobiol Dis. 46(2):336-50 |
| Year | 2012 |