SCA37 DAB1

Spinocerebellar ataxia type 37 (SCA37) is a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1), characterized by a cerebellar syndrome along with altered vertical eye movements¹.

Prevalence

0.20/100,000 specific to Portugal; not yet found in other geographic regions. Founder effect from Iberian Peninsula².

Age of Onset Details

Typical: 33-53; Range: 18-64².

Locus

hg19

chr1:57832716-57832797

hg38

chr1:57367044-57367125

t2t

chr1:57245936-57245977

Details

Pathogenicity only associated with pathogenic motif >30 repeats, flanked by at least 58 repeats of reference motif on either side; reference repeat (AAAAT) can range from 1 to 400 repeats, although typically less than 30². The pathogenic motif is unstable, particularly when transmitted by the father².

Mechanism

GoF

Toxic gain-of-function mechanism in protein, associated with alternative splicing, an RNA switch, and an upregulation of reelin-DAB1 signalling^3,4.

Year

2017⁵

Location in Gene

Intron 1 (most isoforms)

Gene Strand

Alleles

Ref. Motif

AAAAT

Pathogenic (ref.)

GAAAT

Pathogenic (gene)

ATTTC

Unknown (ref.)

AAAAA

Unknown (gene)

TTTTT

gnomAD

Pathogenic Genotype (%): % of individuals predicted to be affected based on their genotype

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0014410

Spinocerebellar Ataxia Type 37

Antoni,Matilla-Dueñas, Victor,Volpini

GeneReviews® · 1993-01-01

genereviews:NBK541729

omim:615945

Spinocerebellar ataxia: an update.

Roisin,Sullivan, Wai Yan,Yau, Emer,O'Connor, Henry,Houlden

Journal of neurology · 2018-10-03

pmid:30284037

A Pentanucleotide ATTTC Repeat Insertion in the Non-coding Region of DAB1, Mapping to SCA37, Causes Spinocerebellar Ataxia.

Ana I,Seixas, Joana R,Loureiro, Cristina,Costa, Andrés,Ordóñez-Ugalde, Hugo,Marcelino, Cláudia L,Oliveira, José L,Loureiro, Ashutosh,Dhingra, Eva,Brandão, Vitor T,Cruz, Angela,Timóteo, Beatriz,Quintáns, Guy A,Rouleau, Patrizia,Rizzu, Ángel,Carracedo, José,Bessa, Peter,Heutink, Jorge,Sequeiros, Maria J,Sobrido, Paula,Coutinho, Isabel,Silveira

American journal of human genetics · 2017-07-06

pmid:28686858

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

Insights into familial adult myoclonus epilepsy pathogenesis: How the same repeat expansion in six unrelated genes may lead to cortical excitability.

Christel,Depienne, Arn M J M,van den Maagdenberg, Theresa,Kühnel, Hiroyuki,Ishiura, Mark A,Corbett, Shoji,Tsuji

Epilepsia · 2023-01-22

pmid:36622139

Familial Cerebellar Ataxia and Amyotrophic Lateral Sclerosis/Frontotemporal Dementia with DAB1 and C9ORF72 Repeat Expansions: An 18-Year Study.

Angela,Rosenbohm, Hendrik,Pott, Mirja,Thomsen, Haloom,Rafehi, Sabine,Kaya, Silke,Szymczak, Alexander E,Volk, Kathrin,Mueller, Isabel,Silveira, Jochen H,Weishaupt, Holger,Tönnies, Philip,Seibler, Katja,Zschiedrich, Susen,Schaake, Ana,Westenberger, Christine,Zühlke, Christel,Depienne, Joanne,Trinh, Albert C,Ludolph, Christine,Klein, Melanie,Bahlo, Katja,Lohmann

Movement disorders : official journal of the Movement Disorder Society · 2022-09-23

pmid:36148898

ATTCT and ATTCC repeat expansions in the ATXN10 gene affect disease penetrance of spinocerebellar ataxia type 10.

C Alejandra,Morato Torres, Faria,Zafar, Yu-Chih,Tsai, Jocelyn Palafox,Vazquez, Michael D,Gallagher, Ian,McLaughlin, Karl,Hong, Jill,Lai, Joyce,Lee, Amanda,Chirino-Perez, Angel Omar,Romero-Molina, Francisco,Torres, Juan,Fernandez-Ruiz, Tetsuo,Ashizawa, Janet,Ziegle, Francisco Javier,Jiménez Gil, Birgitt,Schüle

HGG advances · 2022-08-15

pmid:36092952

Prevalence of

Dona,Aboud Syriani, Darice,Wong, Sameer,Andani, Claudio M,De Gusmao, Yuanming,Mao, May,Sanyoura, Giacomo,Glotzer, Paul J,Lockhart, Sharon,Hassin-Baer, Vikram,Khurana, Christopher M,Gomez, Susan,Perlman, Soma,Das, Brent L,Fogel

Neurology. Genetics · 2020-05-20

pmid:32582864

Mutational mechanism for DAB1 (ATTTC)

Joana R,Loureiro, Cláudia L,Oliveira, Carolina,Mota, Ana F,Castro, Cristina,Costa, José L,Loureiro, Paula,Coutinho, Sandra,Martins, Jorge,Sequeiros, Isabel,Silveira

Human mutation · 2019-01-09

pmid:30588707