SCA8 ATXN8OS

Spinocerebellar ataxia type 8 (SCA8) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I) characterized by cerebellar ataxia and cognitive dysfunction in almost three quarters of patients and pyramidal and sensory signs in approximately a third of patients¹.

Prevalence

0.5 100,000

<1/100,000²; expansion in 1:100-1200 chromosomes³. Found across ethnicities/ancestries, with population-dependent prevalence³.

Age of Onset Details

Typical: 20-40; Range: 0-73³.

Locus

hg19

chr13:70713515-70713561

hg38

chr13:70139383-70139429

t2t

chr13:69361244-69361271

Details

Two genes span the CTG/CAG repeat and are expressed in opposite directions: ATXN8, a nearly pure polyglutamine repeat protein in the CAG direction, and ATXN8OS, which is transcribed to a noncoding CUG repeat RNA⁴. Reduced penetrance is found in alleles of all sizes, although penetrance appears higher at 71+ repeats and repeats at 50-70 appear less likely to result in disease^3,5. Roda et al. suggested that the ATXN8 or ATXN8OS gene should not be evaluated in isolation as a candidate gene for spinocerebellar degenerative disease⁶. CCG/CGG interruptions in high-penetrance SCA8 families increase RAN translation and protein toxicity⁷; Interruptions in CTG/CAG expansion by 1 or more CCG/CGG, CTA/TAG, CTC/GAG, CCA/TGG, or CTT/AAG trinucleotides have been observed in full-penetrance repeats^4,3.

Mechanism

GoF

Polyglutamine/toxic gain-of-function^8,3.

Year

1999⁹

Location in Gene

Exon 1 or 3' UTR depending on transcript

Gene Strand

Alleles

Ref. Motif

CTG

Pathogenic (ref.)

CTG

Pathogenic (gene)

CTG

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0012116

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 8

John Douglas,Cleary, S. H.,Subramony, Laura PW,Ranum

GeneReviews® · 1993-01-01

genereviews:NBK1268

Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8.

Melinda L,Moseley, Tao,Zu, Yoshio,Ikeda, Wangcai,Gao, Anne K,Mosemiller, Randy S,Daughters, Gang,Chen, Marcy R,Weatherspoon, H Brent,Clark, Timothy J,Ebner, John W,Day, Laura P W,Ranum

Nature genetics · 2006-06-25

pmid:16804541

RNA-mediated neurodegeneration in repeat expansion disorders.

Peter K,Todd, Henry L,Paulson

Annals of neurology · 2010-03-01

pmid:20373340

SCA8 should not be tested in isolation for ataxia.

Ricardo H,Roda, Alice B,Schindler, Craig,Blackstone

Neurology. Genetics · 2017-04-21

pmid:28451643

CCG•CGG interruptions in high-penetrance SCA8 families increase RAN translation and protein toxicity.

Barbara A,Perez, Hannah K,Shorrock, Monica,Banez-Coronel, Tao,Zu, Lisa El,Romano, Lauren A,Laboissonniere, Tammy,Reid, Yoshio,Ikeda, Kaalak,Reddy, Christopher M,Gomez, Thomas,Bird, Tetsuo,Ashizawa, Lawrence J,Schut, Alfredo,Brusco, J Andrew,Berglund, Lis F,Hasholt, Jorgen E,Nielsen, S H,Subramony, Laura Pw,Ranum

EMBO molecular medicine · 2021-10-11

pmid:34632710

omim:608768

An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8).

M D,Koob, M L,Moseley, L J,Schut, K A,Benzow, T D,Bird, J W,Day, L P,Ranum

Nature genetics · 1999-04-01

pmid:10192387

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)

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

The Cerebellar Cognitive Affective/Schmahmann Syndrome Scale in Spinocerebellar Ataxias.

Louisa P,Selvadurai, Susan L,Perlman, Tetsuo,Ashizawa, George R,Wilmot, Chiadi U,Onyike, Liana S,Rosenthal, Vikram G,Shakkottai, Henry L,Paulson, Sub H,Subramony, Khalaf O,Bushara, Sheng-Han,Kuo, Cameron,Dietiker, Michael D,Geschwind, Alexandra B,Nelson, Christopher M,Gomez, Puneet,Opal, Theresa A,Zesiewicz, Trevor,Hawkins, Talene A,Yacoubian, Peggy C,Nopoulos, Sharon J,Sha, Peter E,Morrison, Karla P,Figueroa, Stefan M,Pulst, Jeremy D,Schmahmann

Cerebellum (London, England) · 2024-01-02

pmid:38165578

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 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

Prevalence of repeat expansions causing autosomal dominant spinocerebellar ataxias in Hokkaido, the northernmost island of Japan.

Keiichi,Mizushima, Yuka,Shibata, Shinichi,Shirai, Masaaki,Matsushima, Satoko,Miyatake, Ikuko,Iwata, Hiroaki,Yaguchi, Naomichi,Matsumoto, Ichiro,Yabe

Journal of human genetics · 2023-10-17

pmid:37848721

Short tandem repeat expansions in sporadic amyotrophic lateral sclerosis and frontotemporal dementia.

Lyndal,Henden, Liam G,Fearnley, Natalie,Grima, Emily P,McCann, Carol,Dobson-Stone, Lauren,Fitzpatrick, Kathryn,Friend, Lynne,Hobson, Sandrine,Chan Moi Fat, Dominic B,Rowe, Susan,D'Silva, John B,Kwok, Glenda M,Halliday, Matthew C,Kiernan, Srestha,Mazumder, Hannah C,Timmins, Margaret,Zoing, Roger,Pamphlett, Lorel,Adams, Melanie,Bahlo, Ian P,Blair, Kelly L,Williams

Science advances · 2023-05-05

pmid:37146135

Systematic assessment of plasma biomarkers in spinocerebellar ataxia.

Xue-Ning,Shen, Kai-Min,Wu, Yu-Yuan,Huang, Yu,Guo, Shu-Yi,Huang, Ya-Ru,Zhang, Shu-Fen,Chen, Hui-Fu,Wang, Wei,Zhang, Wei,Cheng, Mei,Cui, Qiang,Dong, Jin-Tai,Yu

Neurobiology of disease · 2023-03-30

pmid:37003406

Neuropathology of spinocerebellar ataxia type 8: Common features and unique tauopathy.

Yuki,Yonenobu, Goichi,Beck, Kansuke,Kido, Norihisa,Maeda, Rika,Yamashita, Kimiko,Inoue, Yuko,Saito, Masato,Hasegawa, Hidefumi,Ito, Kazuko,Hasegawa, Eiichi,Morii, Toru,Iwaki, Shigeo,Murayama, Hideki,Mochizuki

Neuropathology : official journal of the Japanese Society of Neuropathology · 2023-01-26

pmid:36703300