Clinical and genetic analysis of three German kindreds with autosomal dominant cerebellar ataxia type I linked to the SCA2 locus

摘要: 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), D12S 1340(1329) yielding a lod score exceeding +3.0 for the combined data. Analysis pedigree provided evidence anticipation as observed in other neurodegenerative disorders due polyglutamine expansion encoded by CAG repeat. This hypothesis confirmed detection SCA2-specific pathological protein 1C2 monoclonal antibody which selectively recognizes large expansions characterization patients. Clinically, were characterized progressive stance, gait limbs. Saccade velocity markedly reduced SCA2. Further oculomotor findings gaze palsy, impaired smooth pursuit optokinetic reflex. Dementia pyramidal tract signs rather rare, while peripheral involvement (reduced or absent ankle reflexes, fasciculation-like movements, amyotrophy) prominent feature. Electrophysiological investigations sensory neuropathy axonal type degeneration posterior columns. Imaging studies demonstrated severe shrinkage brain-stem structures even early stages disease.