title: Clinical behaviour of spinocerebellar ataxia type 12 and intermediate length abnormal CAG repeats in PPP2R2B.
abstract: 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.
authors.affiliation: 1 Neurology Department, Neuroscience Centre, All India Institute of Medical Sciences, New Delhi, India achalsrivastava@hotmail.com faruq.mohd@igib.res.in.
authors.forename: Achal K
authors.initials: AK
authors.lastname: Srivastava
authors.affiliation: 1 Neurology Department, Neuroscience Centre, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Takkar
authors.affiliation: 2 Neuroradiology Department, Neuroscience Centre, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Garg
authors.affiliation: 3 Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology (CSIR -IGIB), Mall Road, Delhi 110007, India achalsrivastava@hotmail.com faruq.mohd@igib.res.in.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Faruq
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D054648:Protein Phosphatase 2 / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D018911:Trinucleotide Repeats / Q000235:genetics*; D055815:Young Adult
chemical_list: D009419:Nerve Tissue Proteins; C505936:PPP2R2B protein, human; D054648:Protein Phosphatase 2
keywords: PPP2R2B; SCA12; autosomal dominant cerebellar ataxia; cerebellum; shortest pathogenic CAG repeats