{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:37:00Z","timestamp":1779367020703,"version":"3.53.0"},"reference-count":26,"publisher":"The Royal Society","issue":"1386","license":[{"start":{"date-parts":[[1999,6,29]],"date-time":"1999-06-29T00:00:00Z","timestamp":930614400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Phil. Trans. R. Soc. Lond. B"],"published-print":{"date-parts":[[1999,6,29]]},"abstract":"<jats:p>Dentatorubral\u2013pallidoluysian atrophy (DRPLA) is an autosomal dominant disorder characterized clinically by myoclonus, epilepsy, cerebellar ataxia, choreoathetosis and dementia. Cardinal pathological features of DRPLA are a combined degeneration of both the dentatorubral and the pallidoluysian systems. Although the early sporadic cases were reported by Western neuropathologists, a strong heritability and an age of onset\u2013dependent variability of the clinical features were carefully deduced by Japanese clinicians. The disease is fairly common in Japan, but extremely rare in Caucasians. Since the gene was identified in 1994, DRPLA is known as one of the CAG repeat expansion diseases, in which the responsible gene is located on chromosome 12p and its product is called atrophin 1. DRPLA shows prominent \u2018anticipation\u2019, which is genetically clearly explained by a marked instability of the expanded CAG repeat length during spermatogenesis. Moreover, the instability of the CAG repeat length also seems to occur in the somatic cells, resulting in \u2018somatic mosaicism\u2019. Possible mechanism(s) underlying the neuronal cell death in DRPLA are discussed in terms of molecular pathological points of view.<\/jats:p>","DOI":"10.1098\/rstb.1999.0460","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T19:55:43Z","timestamp":1027713343000},"page":"1069-1074","source":"Crossref","is-referenced-by-count":21,"title":["Molecular pathology of dentatorubral--pallidoluysian atrophy"],"prefix":"10.1098","volume":"354","author":[{"given":"Ichiro","family":"Kanazawa","sequence":"first","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo 113- 8655, Japan ()"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[1999,6,29]]},"reference":[{"key":"p_1","doi-asserted-by":"crossref","unstructured":"Davies S. W. Turmaine M. Cozens B. A. DiFiglia M. Sharp A. H. Ross C. A. Scherzinger E. Wanker E. E. Mangiarini L. & Bates G. P. 1997 Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90 537^548.","DOI":"10.1016\/S0092-8674(00)80513-9"},{"key":"p_2","doi-asserted-by":"crossref","unstructured":"Duyao M. (and 41 others) 1993 Trinucleotide repeat length instability and age of onset in Huntington's disease. Nature Genet. 4 387^392.","DOI":"10.1038\/ng0893-387"},{"key":"p_3","doi-asserted-by":"crossref","unstructured":"Hashida S. Goto J. Kurisaki H. Mizusawa H. & Kanazawa I. 1997 Brain regional di\u00a1erences in the expansion of a CAG repeat in the spinocerebellar ataxias: dentatorubral ^ pallidoluysian atrophy Machado ^Joseph disease and spinocerebellar ataxia type 1. Ann. Neurol. 41 505^511.","DOI":"10.1002\/ana.410410414"},{"key":"p_4","doi-asserted-by":"crossref","unstructured":"Igarashi S. (and 18 others) 1998 Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch. Nature Genet. 18 111^117.","DOI":"10.1038\/ng0298-111"},{"key":"p_5","doi-asserted-by":"crossref","unstructured":"Ikeuchi T. (and 20 others) 1995 Dentatorubral ^ pallidoluysian atrophy: clinical features are closely related to unstable expansions of trinucleotide (CAG) repeat. Ann. Neurol. 37 769^775.","DOI":"10.1002\/ana.410370610"},{"key":"p_6","doi-asserted-by":"publisher","DOI":"10.1038\/ng0194-9"},{"key":"p_7","doi-asserted-by":"crossref","unstructured":"Komure O. (and 12 others) 1995 DNA analysis in hereditary dentatorubral ^pallidoluysian atrophy: correlation between CAG repeat length and phenotypic variation and the molecular basis of anticipation. Neurology 45 143^149.","DOI":"10.1212\/WNL.45.1.143"},{"key":"p_8","doi-asserted-by":"crossref","unstructured":"Li S. H. McInnis M. G. Margolis R. L. Antonarakis S. E. & Ross C. A. 1993 Novel triplet repeat containing genes in human brain: cloning expression and length polymorphisms. Genomics 16 572^579.","DOI":"10.1006\/geno.1993.1232"},{"key":"p_9","doi-asserted-by":"crossref","unstructured":"Mangiarini L. (and 10 others) 1996 Exon 1 of the HD gene with an expanded CAG repeat is su\u00a4cient to cause a progressive neurological phenotype in transgenic mice. Cell 87 493^506.","DOI":"10.1016\/S0092-8674(00)81369-0"},{"key":"p_10","article-title":"DRPLA gene (atrophin 1) sequence and mRNA expression in human brain","volume":"36","author":"Margolis R. L.","year":"1996","journal-title":"J. Neurol. Sci."},{"key":"p_11","doi-asserted-by":"publisher","DOI":"10.1038\/ng0194-14"},{"key":"p_12","unstructured":"Naito H. 1990 The clinical picture and classi\u00a2cation of dentatorubral^ pallidoluysian atrophy (DRPLA). Shinkei-Naika 32 450^456. (In Japanese.)"},{"key":"p_13","doi-asserted-by":"crossref","unstructured":"Naito H. & Oyanagi S. 1982 Familial myoclonus epilepsy and choreoathetosis: hereditary dentatorubral ^pallidoluysian atrophy. Neurology 32 798^807.","DOI":"10.1212\/WNL.32.8.798"},{"key":"p_14","unstructured":"Naito H. Izawa K. Kurosaki T. Kaji S. & Sawa M. 1972 Progressive myoclonus epilepsy with Mendelian dominant heredity. Psychiat. Neurol. Japon. 74 871^897. (In Japanese.)"},{"key":"p_15","doi-asserted-by":"crossref","unstructured":"Nishiyama K. Nakamura K. Murayama S. Yamada M. & Kanazawa I. 1997 Regional and cellular expression of the dentatorubral ^pallidoluysian atrophy gene in brains of normal and a\u00a1ected individuals. Ann. Neurol. 41 599^605.","DOI":"10.1002\/ana.410410508"},{"key":"p_16","unstructured":"Oyanagi S. 1978 On pathology of the chorea\u00f6with reference to `hereditary pallidal and dentate system atrophy proposed by us. Saishin-Igaku 33 236^242. (In Japanese.)"},{"key":"p_17","doi-asserted-by":"crossref","unstructured":"Perutz M. F. Johnson T. Suzuki M. & Finch J. T. 1994 Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. Proc. Natl Acad. Sci. USA 91 5355^5358.","DOI":"10.1073\/pnas.91.12.5355"},{"key":"p_18","doi-asserted-by":"crossref","unstructured":"Sano A. Yamauchi N. Kakimoto Y. Komure O. Kawai J. Hazama F. Kuzume K. Sano N. & Kondo I. 1994 Anticipation in hereditary dentatorubral ^ pallidoluysian atrophy. Hum. Genet. 93 699^702.","DOI":"10.1007\/BF00201575"},{"key":"p_19","unstructured":"Takahashi H. Yamada M. & Takeda S. 1995 Neuropathology of dentatorubral ^pallidoluysian atrophy and Machado ^ Joseph disease. No-to-Shinkei 47 947^953. (In Japanese.)"},{"key":"p_20","doi-asserted-by":"crossref","unstructured":"Takahata N. Ito K. Yoshimura Y. Nishihori K. & Suzuki H. 1978 Familial chorea and myoclonus epilepsy. Neurology 28 913^919.","DOI":"10.1212\/WNL.28.9.913"},{"key":"p_21","article-title":"Somatic mosaicism of expanded CAG repeats in brains of patients with dentatorubral ^pallidoluysian atrophy: cellular population-dependent dynamics of mitotic instability","volume":"58","author":"Takano H.","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"p_22","doi-asserted-by":"crossref","unstructured":"Titica J. & Van Bogaert L. 1946 Heredo-degenerative hemiballismus. Brain 69 251^263.","DOI":"10.1093\/brain\/69.4.251"},{"key":"p_23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1827.1997.tb04429.x"},{"key":"p_24","doi-asserted-by":"crossref","unstructured":"Yanagisawa H. (and 22 others) 1996 A unique origin and multistep process for the generation of expanded DRPLA triplet repeats. Hum. Mol. 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