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

HP:0000597 Ophthalmoparesis HP:0000639 Nystagmus HP:0000643 Blepharospasm HP:0000726 Dementia HP:0001138 Optic neuropathy HP:0001152 Saccadic smooth pursuit interruptions HP:0001249 Intellectual disability HP:0001250 Seizure HP:0001251 Ataxia HP:0001260 Dysarthria HP:0001265 Hyporeflexia HP:0001266 Choreoathetosis HP:0001300 Parkinsonism HP:0001310 Dysmetria HP:0001332 Dystonia HP:0001336 Myoclonus HP:0002066 Gait ataxia HP:0002070 Limb ataxia HP:0002072 Chorea HP:0002073 Progressive cerebellar ataxia HP:0002075 Dysdiadochokinesis HP:0002078 Truncal ataxia HP:0002172 Postural instability HP:0002345 Action tremor HP:0002354 Memory impairment HP:0004305 Involuntary movements HP:0007047 Atrophy of the dentate nucleus HP:0010831 Impaired proprioception HP:0010867 Dyssynergia HP:0012048 Oromandibular dystonia HP:0030890 Hyperintensity of cerebral white matter on MRI HP:0100543 Cognitive impairment

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. Larger repeat size correlates with a severe epilepsy phenotype. Additionally, repeat size is inversely correlated with age of onset in patients presenting initially with epilepsy, but shows no significant correlation in patients presenting initially with gait instability^2,7.

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 amplify³.

Year

1994⁸

Location in Gene

Coding Exon 5

Gene Strand

Alleles

Ref. Motif

CAG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CAG

Pathogen. (gene)

CAG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interrup. (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

Clinical features of dentatorubral-pallidoluysian atrophy: A survey of Chinese patients.

Na,Zheng, Miao,Li, Yun-Xia,Wang, Guo-En,Yao

The Journal of international medical research · 2026-06-26

pmid:42359808

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