SCA2 ATXN2

A subtype of type I autosomal dominant cerebellar ataxia (ADCA type I) characterized by truncal ataxia, dysarthria, slowed saccades and less commonly ophthalmoparesis and chorea¹.

Prevalence

1.5 100,000

1-2/100,000 (population-dependent)². Cases have been found across ethnicities/ancestries, with population-dependent prevalence³.

Age of Onset Details

Typical: 30-39³; Range: 2-86⁴.

Locus

hg19

chr12:112036754-112036823

hg38

chr12:111598950-111599019

t2t

chr12:111575873-111575940

Details

Full penetrance of single alleles occurs at ~35 repeats^3,5and pathogenic expansions have been documented as large as 500 repeats⁶. 33-34 length repeats are associated with reduced penetrance and later onset (age >50 years)³. Homozygous 31 repeat alleles may lead to recessive disease⁷, while a single 30-32 repeat is associated with increased ALS risk^3,8. Interruptions observed include CAA, CGG, CGC, which appear to stabilize the allele in transmission³. May confer risk for amyotrophic lateral sclerosis⁹.

Mechanism

GoF/LoF

Polyglutamine cytoplasmic aggregates leading to cellular apoptosis; RAN translation implicated³.

Year

1996¹⁰

Location in Gene

Exon 1

Gene Strand

Alleles

Ref. Motif

CTG

Pathogenic (ref.)

CTG

Pathogenic (gene)

AGC

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0008458

Profiling of Short-Tandem-Repeat Disease Alleles in 12,632 Human Whole Genomes.

Haibao,Tang, Ewen F,Kirkness, Christoph,Lippert, William H,Biggs, Martin,Fabani, Ernesto,Guzman, Smriti,Ramakrishnan, Victor,Lavrenko, Boyko,Kakaradov, Claire,Hou, Barry,Hicks, David,Heckerman, Franz J,Och, C Thomas,Caskey, J Craig,Venter, Amalio,Telenti

American journal of human genetics · 2017-11-02

pmid:29100084

Spinocerebellar Ataxia Type 2

Stefan M.,Pulst

GeneReviews® · 1993-01-01

genereviews:NBK1275

omim:183090

The Frequency of Intermediate Alleles in Patients with Cerebellar Phenotypes.

Elena,Capacci, Silvia,Bagnoli, Giulia,Giacomucci, Costanza Maria,Rapillo, Alessandra,Govoni, Valentina,Bessi, Cristina,Polito, Irene,Giotti, Alice,Brogi, Elisabetta,Pelo, Sandro,Sorbi, Benedetta,Nacmias, Camilla,Ferrari

Cerebellum (London, England) · 2023-10-31

pmid:37906407

Childhood-onset ataxia: testing for large CAG-repeats in SCA2 and SCA7.

Rong,Mao, Arthur S,Aylsworth, Nicholas,Potter, William G,Wilson, Galen,Breningstall, Myra J,Wick, Dusica,Babovic-Vuksanovic, Martha,Nance, Marc C,Patterson, Christopher M,Gomez, Karen,Snow

American journal of medical genetics · 2002-07-15

pmid:12116207

Homozygous 31 trinucleotide repeats in the SCA2 allele are pathogenic for cerebellar ataxia.

Maya,Tojima, Gaku,Murakami, Rie,Hikawa, Hodaka,Yamakado, Hirofumi,Yamashita, Ryosuke,Takahashi, Masaru,Matsui

Neurology. Genetics · 2018-10-16

pmid:30533529

Amyotrophic lateral sclerosis risk for spinocerebellar ataxia type 2 ATXN2 CAG repeat alleles: a meta-analysis.

Annalese G,Neuenschwander, Khanh K,Thai, Karla P,Figueroa, Stefan M,Pulst

JAMA neurology · 2014-12-01

pmid:25285812

Gijs H P,Tazelaar, Steven,Boeynaems, Mathias,De Decker, Joke J F A,van Vugt, Lindy,Kool, H Stephan,Goedee, Russell L,McLaughlin, William,Sproviero, Alfredo,Iacoangeli, Matthieu,Moisse, Maarten,Jacquemyn, Dirk,Daelemans, Annelot M,Dekker, Rick A,van der Spek, Henk-Jan,Westeneng, Kevin P,Kenna, Abdelilah,Assialioui, Nica,Da Silva, Mónica,Povedano, Jesus S Mora,Pardina, Orla,Hardiman, François,Salachas, Stéphanie,Millecamps, Patrick,Vourc'h, Philippe,Corcia, Philippe,Couratier, Karen E,Morrison, Pamela J,Shaw, Christopher E,Shaw, R Jeroen,Pasterkamp, John E,Landers, Ludo,Van Den Bosch, Wim,Robberecht, Ammar,Al-Chalabi, Leonard H,van den Berg, Philip,Van Damme, Jan H,Veldink, Michael A,van Es

Brain communications · 2020-05-19

pmid:32954321

Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT.

K,Sanpei, H,Takano, S,Igarashi, T,Sato, M,Oyake, H,Sasaki, A,Wakisaka, K,Tashiro, Y,Ishida, T,Ikeuchi, R,Koide, M,Saito, A,Sato, T,Tanaka, S,Hanyu, Y,Takiyama, M,Nishizawa, N,Shimizu, Y,Nomura, M,Segawa, K,Iwabuchi, I,Eguchi, H,Tanaka, H,Takahashi, S,Tsuji

Nature genetics · 1996-11-01

pmid:8896556

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)

Screening for SCA27B, CANVAS and other repeat expansion disorders in Greek patients with late-onset cerebellar ataxia suggests a need to update current diagnostic algorithms.

Georgios,Koutsis, Chrisoula,Kartanou, Zoi,Kontogeorgiou, Chrysoula,Koniari, Alexandros,Mitrousias, David,Pellerin, Marie-Jose,Dicaire, Pablo,Iruzubieta, Matt C,Danzi, Konstantinos,Athanassopoulos, Nikolaos,Ragazos, Maria,Stamelou, Michail,Rentzos, Evangelos,Anagnostou, Stephan,Zuchner, Bernard,Brais, Henry,Houlden, Marios,Panas, Leonidas,Stefanis, Georgia,Karadima

Journal of the neurological sciences · 2024-11-15

pmid:39571249

Post-symptomatic administration of hMSCs exerts therapeutic effects in SCA2 mice.

Sehwan,Kim, Chanchal,Sharma, Jungwan,Hong, Jong-Heon,Kim, Youngpyo,Nam, Min Sung,Kim, Tae Yong,Lee, Kyung-Suk,Kim, Kyoungho,Suk, Ho-Won,Lee, Sang Ryong,Kim

Stem cell research & therapy · 2024-11-09

pmid:39521966

Progressive Apraxia of Speech as a Manifestation of Spinocerebellar Ataxia 2: Case Report.

Audrey M,Blazek, Gabriela,Meade, Lauren M,Jackson, Ralitza,Gavrilova, Julie,Stierwalt, Jennifer M,Martinez-Thompson, Joseph R,Duffy, Heather,Clark, Mary M,Machulda, Jennifer L,Whitwell, Keith A,Josephs, Rene L,Utianski, Hugo,Botha

Neurology. Genetics · 2024-11-01

pmid:39512795

Fluctuations in Medium Viscosity May Affect the Stability of the CAG Tract in the

Anna,Dorohova, Oksana,Lyasota, Stepan,Dzhimak, Alexandr,Svidlov, Olga,Leontyeva, Mikhail,Drobotenko

Biomedicines · 2024-10-19

pmid:39457708

Parkinson's families project: a UK-wide study of early onset and familial Parkinson's disease.

Clodagh,Towns, Zih-Hua,Fang, Manuela M X,Tan, Simona,Jasaityte, Theresa M,Schmaderer, Eleanor J,Stafford, Miriam,Pollard, Russel,Tilney, Megan,Hodgson, Lesley,Wu, Robyn,Labrum, Jason,Hehir, James,Polke, Lara M,Lange, Anthony H V,Schapira, Kailash P,Bhatia, Andrew B,Singleton, Cornelis,Blauwendraat, Christine,Klein, Henry,Houlden, Nicholas W,Wood, Paul R,Jarman, Huw R,Morris, Raquel,Real

NPJ Parkinson's disease · 2024-10-17

pmid:39420034

Spinocerebellar Ataxia in Brazil: A Comprehensive Genotype - Phenotype Analysis.

Maria Carolina Da,Cunha Ganimi, Christian Marques,Couto, Alessandra de,La Rocque Ferreira, Carmen Lucia,Antão Paiva

Cerebellum (London, England) · 2024-09-25

pmid:39317855

ATAXIN-2 intermediate-length polyglutamine expansions elicit ALS-associated metabolic and immune phenotypes.

Renata,Vieira de Sá, Emma,Sudria-Lopez, Marta,Cañizares Luna, Oliver,Harschnitz, Dianne M A,van den Heuvel, Sandra,Kling, Danielle,Vonk, Henk-Jan,Westeneng, Henk,Karst, Lauri,Bloemenkamp, Suzy,Varderidou-Minasian, Domino K,Schlegel, Mayte,Mars, Mark H,Broekhoven, Nicky C H,van Kronenburg, Youri,Adolfs, Vamshidhar R,Vangoor, Rianne,de Jongh, Tijana,Ljubikj, Lianne,Peeters, Sabine,Seeler, Enric,Mocholi, Onur,Basak, David,Gordon, Fabrizio,Giuliani, Tessa,Verhoeff, Giel,Korsten, Teresa,Calafat Pla, Morten T,Venø, Jørgen,Kjems, Kevin,Talbot, Michael A,van Es, Jan H,Veldink, Leonard H,van den Berg, Pavol,Zelina, R Jeroen,Pasterkamp

Nature communications · 2024-08-29

pmid:39209824

Stability of the CAG Tract in the

Oksana,Lyasota, Anna,Dorohova, Jose Luis,Hernandez-Caceres, Alexandr,Svidlov, Elena,Tekutskaya, Mikhail,Drobotenko, Stepan,Dzhimak

Biomedicines · 2024-07-24

pmid:39200113

Spinocerebellar Ataxias: Phenotypic Spectrum of PolyQ versus Non-Repeat Expansion Forms.

João,Moura, Jorge,Oliveira, Mariana,Santos, Sara,Costa, Lénia,Silva, Carolina,Lemos, José,Barros, Jorge,Sequeiros, Joana,Damásio

Cerebellum (London, England) · 2024-07-24

pmid:39048885