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

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