Clinical and genetic analysis of three German kindreds with autosomal dominant cerebellar ataxia type I linked to the SCA2 locus.
J Neurol. 1997-04-01; 244(4): 256-261
DOI: 10.1007/s004150050081
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1. J Neurol. 1997 Apr;244(4):256-61.
Clinical and genetic analysis of three German kindreds with autosomal dominant
cerebellar ataxia type I linked to the SCA2 locus.
Bürk K(1), Stevanin G, Didierjean O, Cancel G, Trottier Y, Skalej M, Abele M,
Brice A, Dichgans J, Klockgether T.
Author information:
(1)Department of Neurology, University of Tübingen, Germany.
The detailed clinical, electrophysiological and imaging data of three German
autosomal dominant cerebellar ataxia (ADCA) families are reported. Linkage to
SCA2 was established using microsatellite markers D12S105, D12S1339(1328),
D12S1304(1329) yielding a lod score exceeding +3.0 for the combined data.
Analysis of the pedigree data provided evidence of anticipation as observed in
other neurodegenerative disorders due to polyglutamine expansion encoded by a CAG
repeat. This hypothesis was confirmed by the detection of the SCA2-specific
pathological protein using the 1C2 monoclonal antibody which selectively
recognizes large polyglutamine expansions and the characterization of a CAG
expansion in the patients. Clinically, the families were characterized by
progressive ataxia of stance, gait and limbs. Saccade velocity was markedly
reduced in SCA2. Further oculomotor findings were gaze palsy, impaired smooth
pursuit and reduced optokinetic reflex. Dementia and pyramidal tract signs were
rather rare, while peripheral involvement (reduced or absent ankle reflexes,
fasciculation-like movements, amyotrophy) was a prominent feature.
Electrophysiological investigations provided evidence of sensory neuropathy of
the axonal type and degeneration of the posterior columns. Imaging studies
demonstrated severe shrinkage of brain-stem structures even in early stages of
the disease.
DOI: 10.1007/s004150050081
PMID: 9112595 [Indexed for MEDLINE]