Spinocerebellar ataxia type 2. Genotype and phenotype in German kindreds
L. Schols, S. Gispert, M. Vorgerd, A. M. Menezes Vieira-Saecker, P. Blanke, G. Auburger, G. Amoiridis, S. Meves, J. T. Epplen, H. Przuntek, S. M. Pulst and O. Riess
Department of Neurology, St Josef Hospital, Bochum, Germany.
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.
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Rub et al.
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