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Nat Genet. 2006 Feb;38(2):184-90. Epub 2006 Jan 22.

Spectrin mutations cause spinocerebellar ataxia type 5.

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  • 1Department of Genetics, Cell Biology, and Development, University of Minnesota, 321 Church St. SE, Minneapolis, Minnesota 55455 USA.

Abstract

We have discovered that beta-III spectrin (SPTBN2) mutations cause spinocerebellar ataxia type 5 (SCA5) in an 11-generation American kindred descended from President Lincoln's grandparents and two additional families. Two families have separate in-frame deletions of 39 and 15 bp, and a third family has a mutation in the actin/ARP1 binding region. Beta-III spectrin is highly expressed in Purkinje cells and has been shown to stabilize the glutamate transporter EAAT4 at the surface of the plasma membrane. We found marked differences in EAAT4 and GluRdelta2 by protein blot and cell fractionation in SCA5 autopsy tissue. Cell culture studies demonstrate that wild-type but not mutant beta-III spectrin stabilizes EAAT4 at the plasma membrane. Spectrin mutations are a previously unknown cause of ataxia and neurodegenerative disease that affect membrane proteins involved in glutamate signaling.

PMID:
16429157
[PubMed - indexed for MEDLINE]
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