title: Spinocerebellar ataxia type 2. Genotype and phenotype in German kindreds.
abstract: BACKGROUND
  Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant cerebellar ataxia (ADCA) for which the disease-causing mutation has recently been characterized as an expanded CAG trinucleotide repeat. We investigated 64 families of German ancestry with ADCA and 55 patients with sporadic ataxia for the SCA2 mutation.
  
  
  RESULTS
  Expanded alleles were found in 6 of the 64 families and in 1 patient with sporadic ataxia. This patient had a de novo mutation from an intermediate paternal allele. Length of repeats in 21 patients with SCA2 ranged from 36 to 52 CAG motifs and was inversely correlated with age at onset and progression of the disease. Expanded alleles were unstable during meiosis; paternal transmission especially caused significant anticipation of onset up to 26 years earlier. The SCA2 phenotype differed from those of SCA1 and SCA3 with higher frequencies of slowed ocular movements, postural and action tremor, myoclonus, and hyporeflexia. However, no single feature was sufficient to permit a specific clinical diagnosis.
  
  
  CONCLUSIONS
  Spinocerebellar ataxia type 2 accounts for about 10% of German families with ADCA but may also be present in sporadic ataxia due to de novo mutations. Clinical features are highly variable among and even within families. However, the size of the expanded repeat influences the phenotype and is relevant for course and prognosis of the disease.
authors.affiliation: Department of Neurology, St Josef Hospital, Bochum, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Schöls
authors.forename: S
authors.initials: S
authors.lastname: Gispert
authors.forename: M
authors.initials: M
authors.lastname: Vorgerd
authors.forename: A M
authors.initials: AM
authors.lastname: Menezes Vieira-Saecker
authors.forename: P
authors.initials: P
authors.lastname: Blanke
authors.forename: G
authors.initials: G
authors.lastname: Auburger
authors.forename: G
authors.initials: G
authors.lastname: Amoiridis
authors.forename: S
authors.initials: S
authors.lastname: Meves
authors.forename: J T
authors.initials: JT
authors.lastname: Epplen
authors.forename: H
authors.initials: H
authors.lastname: Przuntek
authors.forename: S M
authors.initials: SM
authors.lastname: Pulst
authors.forename: O
authors.initials: O
authors.lastname: Riess
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001921:Brain / Q000473:pathology; D002648:Child; D003679:Deglutition; D004594:Electrophysiology; D005121:Extremities / Q000503:physiopathology; D005260:Female; D005684:Gait; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012021:Reflex, Abnormal; D013132:Spinocerebellar Degenerations / Q000145:classification / Q000235:genetics* / Q000503:physiopathology