Clinical behaviour of spinocerebellar ataxia type 12 and intermediate length abnormal CAG repeats in PPP2R2B.
Spinocerebellar ataxia type 12 (SCA12) is a rare neurodegenerative disorder caused by CAG repeat expansion in the PPP2R2B gene. Previously, the causal length of CAG repeats ascribed to SCA12 was more than 51; however, a few reports have also described unusual occurrence of CAG repeat length 36-51 repeats among patients of different geographical population, with atypical clinical association. From our systematic search for SCA12 in a genetic screening programme, we have identified a large number of SCA12 cases. In this study, we specifically describe the clinical behaviour of 18 patients who harbour CAG repeats in the range of 43-50 and compare their clinical behaviour with patients carrying typical pathogenic threshold length of 51 CAG repeats. Unsurprisingly, we observed that the clinical characteristics were similar to those of typical SCA12 phenotype, with large variability in the age at onset. Radiologically, we observed a variable degree of cerebro-cerebellar degeneration along with white matter changes that do not correlate with the disease severity. We define a new pathogenic threshold of CAG-43 to be pathogenic for SCA12 diagnosis and also describe the clinical profiles of two biallelic CAG expansion carriers. We also propose that SCA12 might not be that restricted in terms of occurrence in other geographical or ethnic populations, as it was previously presumed to be.
['Srivastava|Achal K|AK|', 'Takkar|Amit|A|', 'Garg|Ajay|A|', 'Faruq|Mohammed|M|']
D000328:Adult D017668:Age of Onset D000368:Aged D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D009419:Nerve Tissue Proteins D010375:Pedigree D010641:Phenotype D054648:Protein Phosphatase 2 D020754:Spinocerebellar Ataxias D018911:Trinucleotide Repeats D055815:Young Adult
SCA12 PPP2R2B autosomal dominant cerebellar ataxia cerebellum shortest pathogenic CAG repeats