Autosomal dominant SCA5 and autosomal recessive infantile SCA are allelic conditions resulting from SPTBN2 mutations

Solaf M. Elsayed, Raoul Heller, Michaela Thoenes, Maha S. Zaki, Daniel Swan, Ezzat Elsobky, Christine Zühlke, Inga Ebermann, Gudrun Nürnberg, Peter Nürnberg, Hanno J. Bolz*

*Korrespondierende/r Autor/-in für diese Arbeit
13 Zitate (Scopus)

Abstract

Although many genes have been identified for the autosomal recessive cerebellar ataxias (ARCAs), several patients are unlinked to the respective loci, suggesting further genetic heterogeneity. We combined homozygosity mapping and exome sequencing in a consanguineous Egyptian family with congenital ARCA, mental retardation and pyramidal signs. A homozygous 5-bp deletion in SPTBN2, the gene whose in-frame mutations cause autosomal dominant spinocerebellar ataxia type 5, was shown to segregate with ataxia in the family. Our findings are compatible with the concept of truncating SPTBN2 mutations acting recessively, which is supported by disease expression in homozygous, but not heterozygous, knockout mice, ataxia in Beagle dogs with a homozygous frameshift mutation and, very recently, a homozygous SPTBN2 nonsense mutation underlying infantile ataxia and psychomotor delay in a human family. As there was no evidence for mutations in 23 additional consanguineous families, SPTBN2-related ARCA is probably rare.

OriginalspracheEnglisch
ZeitschriftEuropean Journal of Human Genetics
Jahrgang22
Ausgabenummer2
Seiten (von - bis)286-288
Seitenumfang3
ISSN1018-4813
DOIs
PublikationsstatusVeröffentlicht - 01.02.2014

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