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. Epilepsy is common in earlier onset cases².

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 Australia³.

Age of Onset

Typical: 20-40^4,3. Range: 0⁵- 72³.

HPO Terms

–

Association

Mendelian

Locus

hg19 chr12:7045879-7045938

hg38 chr12:6936716-6936775

t2t chr12:6947903-6947941

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 transmission³. CAA interruptions have been observed without known clinical association⁶. Length of the repeat is inversely associated with age of onset and severe epilepsy phenotype².

Mechanism

GoF

Polyglutamine expansions leading to gain of function³.

Detection

PCR fragment analysis has detected most moderate alleles, but Southern blotting or RP-PCR have been used in cases of large expansions or when PCR shows an apparently homozygous small allele, to exclude allelic dropout of a larger expansion that failed to amplify [@genereviews:NBK1491].

Year

1994⁷

Location in Gene

Coding Exon 5

Gene Strand

Alleles

Ref. Motif

CAG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CAG

Pathogenic (gene)

AGC

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0007435

Epilepsy in dentatorubral-pallidoluysian atrophy: A systematic review and meta-analysis.

Toru,Horinouchi, Haruka,Ishibashi, Yukako,Nakagami, Yoko,Kobayashi Takahashi, Takato,Akiba, Masaharu,Miyauchi, Naohiro,Yamamoto, Ryoichi,Inoue, Satoshi,Kodama, Takafumi,Kubota, Naoto,Kuroda

Epilepsia · 2025-10-28

pmid:41147955

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)

Computational Short Tandem Repeat Genotyping Reveals Clinically Relevant Expansions in a Large Turkish Neurodegeneration Disease Cohort.

Zakhiriddin,Khojakulov, Robin J,Palvadeau, Müge,Kovancılar-Koç, Irmak,Atay, Irmak,Şahbaz, Şeyma,Tekgül, Ayça,Şahin, Esmer Zeynep Duru,Badakal, Tuğçe,Gül-Demirkale, Vildan,Çiftçi, Elif,Bayraktar, Ceren,Tunca, Natalia,Smolina, Fulya,Akçimen, Ayşe Nazlı,Başak

International journal of molecular sciences · 2026-05-13

pmid:42196324

Atrophin-1 antisense oligonucleotide provides robust protection from pathology in a fully humanized DRPLA model.

Velvet L,Smith, Bereket Z,Gidi, Robert M,Bragg, Jeffrey P,Cantle, Aliza,Ben-Varon, Briana,Noble, Silvia,Prades, Andrea,Compton, Julie,Greenfield, Joanna A,Korecka, Anya,Gemos, Timothy,Yu, Vikram,Khurana, Holly B,Kordasiewicz, Hien T,Zhao, Melissa,Barker-Haliski, Daniel D,Child, Jeffrey B,Carroll

Molecular therapy. Nucleic acids · 2025-12-31

pmid:41624332

Disrupted Transcriptional Networks in Mammalian Cells Stably Over-Expressing Pathogenic Atrophin-1.

Oluwademilade,Nuga, Masoumeh,Pourhadi, Julia P,Rausch, Sokol V,Todi

Journal of neuroscience research · 2025-12-01

pmid:41355374

Unbiased human genomic characterization of polyglutamine disorder genes to guide biological understanding and therapeutic strategies.

Kevin Lucy,Namuli, Britt I,Drögemöller, Galen E B,Wright

HGG advances · 2025-11-17

pmid:41254939

The genetic landscape of spinocerebellar ataxias in Taiwan: Insights from 876 genetically confirmed cases.

Shih-Chun,Lan, Cheng-Tsung,Hsiao, Kang-Yang,Jih, Yi-Chu,Liao, Yi-Chung,Lee

Parkinsonism & related disorders · 2025-10-12

pmid:41082794

Disrupted Transcriptional Networks by Mutant Atrophin-1 in a Cell Culture Model of Dentatorubral-Pallidoluysian Atrophy.

Oluwademilade,Nuga, Masoumeh,Pourhadi, Julia P,Rausch, Sokol V,Todi

bioRxiv : the preprint server for biology · 2025-08-12

pmid:40832356

Diagnostic yield and limitations of whole-genome sequencing for hereditary cerebellar ataxia.

Wai Yan,Yau, Roisin,Sullivan, Emer,O'Connor, David,Pellerin, Michael H,Parkinson, Paola,Giunti, Marie-Josée,Dicaire, Matt C,Danzi, Stephan,Züchner, Bernard,Brais, Nicholas W,Wood, Henry,Houlden, Jana,Vandrovcova

Brain communications · 2025-05-17

pmid:40488180

Accurate Quantification of Mutant and Wild-Type polyQ Proteins Using Simple Western Capillary Immunoassays.

Bas,Röttgering, Janwillem,Testerink, Rudie,Weij, Chantal,Beekman, Nicole,Datson

Molecular neurobiology · 2025-05-31

pmid:40450087

Approach to Progressive Myoclonic Epilepsies: Clinical Clues for Genetic Testing.

Prasanthi,Aripirala, Sujit Abajirao,Jagtap

Journal of child neurology · 2025-05-08

pmid:40340521

Locus DRPLA ATN1

Disease

Locus

Alleles

gnomAD

References

Additional Literature