Spectrin mutations in spinocerebellar ataxia (SCA).
Recently, betaIII spectrins have been recognized as ataxia disease genes, with the identification by Ikeda and co-workers of pathogenic mutations in the SPTBN2 gene in three large (and mapped) SCA5 families of American and European origin.((1)) With their discovery, the large "Lincoln" family has been traced back to the underlying genetic defect for the slowly progressive cerebellar ataxia. In addition, the involvement of this component of the cytoskeleton directs attention towards the possible role of organelle stability during neurodegeneration. The findings suggest that the mechanical properties of neurons and their dynamics may be as important as altered Ca(2+) homeostasis, transcriptional dysregulation, and impaired protein degradation in neurodegeneration conditions.
Bauer
Peter
P
Department of Medical Genetics, University of Tübingen, Germany.
Schöls
Ludger
L
Riess
Olaf
O
D006801:Humans; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics; D013049:Spectrin / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000235:genetics*
C495133:SPTBN2 protein, human; D013049:Spectrin