Why is SCA12 different from other SCAs?
Spinocerebellar ataxia type 12 (SCA12), now described in European-American and Asian (Indian) pedigrees, is unique among the SCAs from clinical, pathological, and molecular perspectives. Clinically, the distinguishing feature is early and prominent action tremor with variability in other signs. Pathologically, brain MRIs also suggest variability, with prominent cortical as well as cerebellar atrophy. Genetically, SCA12 is caused by a CAG repeat expansion that does not encode polyglutamine; we speculate that the mutation may affect expression of the gene PPP2R2B, which encodes a brain-specific regulatory subunit of the protein phosphatase PP2A.
Holmes
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Department of Psychiatry, Hopkins University School of Medicine, Baltimore, MD, USA. seholmes@jhmi.edu
O'Hearn
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Margolis
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RL
D000483:Alleles; D002525:Cerebellar Cortex / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D005192:Family Health; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010375:Pedigree; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics; D020836:Protein Structure, Quaternary; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
D010749:Phosphoprotein Phosphatases