title: Spinocerebellar ataxia type 12.
abstract: SCA12 is a late-onset, autosomal dominant, slowly progressive disorder. Action tremor is the usual presenting sign. Subsequent development of ataxia and hyperreflexia suggests spinocerebellar ataxia. In the index SCA12 kindred, which resides in North America and is of German ancestry, parkinsonism, anxiety, depression, and cognitive dysfunction are not uncommon. SCA12 is linked to a CAG repeat expansion mutation in exon 7 of PPP2R2B, a gene that encodes Bβ, a regulatory subunit of protein phosphatase 2A (PP2A). CAG repeats number 7-28 in normal individuals and 55-78 in SCA12 patients. The mechanism by which this mutation leads to SCA12 has not been determined. The CAG expansion in PPP2R2B has promoter function in vitro. CAG length correlates with increased Bβ expression. There is no evidence that this CAG expansion results in polyglutamine production. In addition to the North. American SCA12 kindred, multiple SCA12 families have been found in Northern India that are not related to the index SCA12 kindred. SCA12 has been reported, rarely, in Singapore and China. Action tremor, anxiety, and depression in SCA12 have responded to usual treatments for these disorders. SCA12 may be considered in patients who present with action tremor and later develop signs of cerebellar and cortical dysfunction.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. eohearn@jhmi.edu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: O'Hearn
authors.forename: Susan E
authors.initials: SE
authors.lastname: Holmes
authors.forename: Russell L
authors.initials: RL
authors.lastname: Margolis
mesh_terms: D005192:Family Health; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D059906:Neuroimaging / Q000379:methods; D054648:Protein Phosphatase 2 / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000175:diagnosis / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins; C505936:PPP2R2B protein, human; D054648:Protein Phosphatase 2