SCA12: an unusual mutation leads to an unusual spinocerebellar ataxia.
Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant neurodegenerative disorder which has been described in pedigrees of German American and Indian descent. The phenotype typically begins with tremor in the fourth decade, progressing to include ataxia and other cerebellar and cortical signs. SCA12 is associated with an expansion of a CAG repeat in the 5' region of the gene PPP2R2B which encodes a brain-specific regulatory subunit of the protein phosphatase PP2A. The repeat size ranges from 55 to 78 triplets in the mutant allele of affected individuals, and from 9 to 28 triplets in normal alleles. It is possible that an expansion mutation in PPP2R2B may influence PPP2R2B expression, perhaps altering the activity of PP2A, an enzyme implicated in multiple cellular functions, including cell cycle regulation, tau phosphorylation, and apoptosis.
Holmes
S E
SE
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. seholmes@jhmi.edu
Hearn
E O
EO
Ross
C A
CA
Margolis
R L
RL
D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D018911:Trinucleotide Repeats
D010749:Phosphoprotein Phosphatases