DRPLA ATN1

Dentatorubral pallidoluysian atrophy (DRPLA) is a rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I). It is characterized by involuntary movements, ataxia, epilepsy, mental disorders, cognitive decline and prominent anticipation¹.

Prevalence

4.5 1,000,000

2-7/1,000,000. More prevalent in Japanese populations; also reported in North America, South America, Europe, and Australia².

Age of Onset Details

Typical: 20-40^3,2. Range: 0⁴- 72².

Locus

hg19

chr12:7045880-7045938

hg38

chr12:6936717-6936775

t2t

chr12:6947904-6947941

Details

Pathogenic expansions (48-93) are fully penetrant with the exception of one documented case of 51 repeats; intermediate alleles (36-47) are associated with a milder phenotype and can expand upon transmission². CAA interruptions have been observed without known clinical association⁵.

Mechanism

GoF

Polyglutamine expansions leading to gain of function².

Year

1994⁶

Location in Gene

Exon 5

Gene Strand

Alleles

Ref. Motif

CAG

Pathogenic (ref.)

CAG

Pathogenic (gene)

AGC

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0007435

DRPLA

Silvia,Prades, Claudio,Melo de Gusmao, Silvia,Grimaldi, Yael,Shiloh-Malawsky, Thomas,Felton, Henry,Houlden

GeneReviews® · 1993-01-01

genereviews:NBK1491

Familial myoclonus epilepsy and choreoathetosis: hereditary dentatorubral-pallidoluysian atrophy.

H,Naito, S,Oyanagi

Neurology · 1982-08-01

pmid:6808417

Severe infantile dentatorubral pallidoluysian atrophy with extreme expansion of CAG repeats.

Y,Shimojo, Y,Osawa, M,Fukumizu, S,Hanaoka, H,Tanaka, F,Ogata, M,Sasaki, K,Sugai

Neurology · 2001-01-23

pmid:11160976

Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing.

Igor,Stevanovski, Sanjog R,Chintalaphani, Hasindu,Gamaarachchi, James M,Ferguson, Sandy S,Pineda, Carolin K,Scriba, Michel,Tchan, Victor,Fung, Karl,Ng, Andrea,Cortese, Henry,Houlden, Carol,Dobson-Stone, Lauren,Fitzpatrick, Glenda,Halliday, Gianina,Ravenscroft, Mark R,Davis, Nigel G,Laing, Avi,Fellner, Marina,Kennerson, Kishore R,Kumar, Ira W,Deveson

Science advances · 2022-03-04

pmid:35245110

Structure and expression of the gene responsible for the triplet repeat disorder, dentatorubral and pallidoluysian atrophy (DRPLA).

S,Nagafuchi, H,Yanagisawa, E,Ohsaki, T,Shirayama, K,Tadokoro, T,Inoue, M,Yamada

Nature genetics · 1994-10-01

pmid:7842016

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

IRF2BPL-Related Disorder, Causing Neurodevelopmental Disorder with Regression, Abnormal Movements, Loss of Speech and Seizures (NEDAMSS) Is Characterized by Pathology Consistent with DRPLA.

Sunita,Venkateswaran, Jean,Michaud, Yoko,Ito, Michael,Geraghty, Evan C,Lewis, Benjamin,Ellezam, Kym M,Boycott, David A,Dyment, Kristin D,Kernohan

Movement disorders : official journal of the Movement Disorder Society · 2024-09-03

pmid:39224955

Tremor-associated short tandem repeat intermediate and pathogenic expansions in familial essential tremor.

Xun,Zhou, Runcheng,He, Sheng,Zeng, Mingqiang,Li, Hongxu,Pan, Yuwen,Zhao, Zhenhua,Liu, Qian,Xu, Jifeng,Guo, Xinxiang,Yan, Jinchen,Li, Beisha,Tang, Qiying,Sun

Brain communications · 2024-06-29

pmid:38961870

Early-onset familial essential tremor is associated with nucleotide expansions of spinocerebellar ataxia in China.

Zhilin,Zheng, Zeyu,Zhu, Jiali,Pu, Chen,Zhou, Lanxiao,Cao, Dayao,Lv, Jinyu,Lu, Gaohua,Zhao, Yanxing,Chen, Jun,Tian, Xinzhen,Yin, Baorong,Zhang, Yaping,Yan, Guohua,Zhao

Molecular biology reports · 2024-01-16

pmid:38227102

Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis.

Yufen,Peng, Qi,Tu, Yao,Han, Liang,Gao, Chenyi,Wan

Open life sciences · 2023-12-12

pmid:38152578

The relationship between the number of CAG repeats and clinical manifestations: a survey of Chinese DRPLA family.

Sujuan,Sun, Wei,Zhao, Xuewu,Liu

Acta neurologica Belgica · 2023-05-27

pmid:37243799

Fast and reliable detection of repeat expansions in spinocerebellar ataxia using exomes.

Jean-Loup,Méreaux, Claire-Sophie,Davoine, Marie,Coutelier, Léna,Guillot-Noël, Anna,Castrioto, Perrine,Charles, Giulia,Coarelli, Claire,Ewenczyk, Stephan,Klebe, Anna,Heinzmann, Aurélie,Méneret, Anne-Laure,Fauret-Amsellem, Jean-Madeleine,de Sainte Agathe, Alexis,Brice, Alexandra,Durr

Journal of medical genetics · 2023-01-04

pmid:36599645

Diagnostic Efficacy of Genetic Studies in a Series of Hereditary Cerebellar Ataxias in Eastern Spain.

Raquel,Baviera-Muñoz, Lidón,Carretero-Vilarroig, Juan Francisco,Vázquez-Costa, Carlos,Morata-Martínez, Marina,Campins-Romeu, Nuria,Muelas, Isabel,Sastre-Bataller, Irene,Martínez-Torres, Julia,Pérez-García, Rafael,Sivera, Teresa,Sevilla, Juan J,Vilchez, Teresa,Jaijo, Carmen,Espinós, Jose M,Millán, Luis,Bataller, Elena,Aller

Neurology. Genetics · 2022-11-14

pmid:36530930

Whole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK: a retrospective diagnostic accuracy and prospective clinical validation study.

Kristina,Ibañez, James,Polke, R Tanner,Hagelstrom, Egor,Dolzhenko, Dorota,Pasko, Ellen Rachel Amy,Thomas, Louise C,Daugherty, Dalia,Kasperaviciute, Katherine R,Smith, Zandra C,Deans, Sue,Hill, Tom,Fowler, Richard H,Scott, John,Hardy, Patrick F,Chinnery, Henry,Houlden, Augusto,Rendon, Mark J,Caulfield, Michael A,Eberle, Ryan J,Taft, Arianna,Tucci

The Lancet. Neurology · 2022-03-01

pmid:35182509

CAG repeat-binding small molecule improves motor coordination impairment in a mouse model of Dentatorubral-pallidoluysian atrophy.

Yuhei,Hasuike, Hana,Tanaka, Terence,Gall-Duncan, Mustafa,Mehkary, Kazuhiko,Nakatani, Christopher E,Pearson, Shoji,Tsuji, Hideki,Mochizuki, Masayuki,Nakamori

Neurobiology of disease · 2021-12-28

pmid:34968706