Clinical and genetic characterizations of 16q-linked autosomal dominant spinocerebellar ataxia (AD-SCA) and frequency analysis of AD-SCA in the Japanese population.

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Autosomal dominant spinocerebellar ataxias (AD -SCAs ) form a clinically and genetically heterogeneous group of neurodegenerative disorders . Recently , a single nucleotide substitution in the 5 '-untranslated region of the puratrophin-1 gene was found to be associated with one type of AD -SCA linked to chromosome 16 q (16 q-SCA ). To obtain further insight into the contribution of the C-to -T substitution in the puratrophin-1 gene to the clinical and genetic characteristics of patients with 16 q-SCA , we analyzed 686 families with 719 individuals diagnosed with progressive ataxia . We found C-to -T substitution in the puratrophin-1 gene in 57 unrelated families with 65 affected individuals . The mean age at onset in the patients with 16 q-SCA was 59 .1 (range , 46 -77 ). Ataxia is the most common initial symptom . The elderly patients over 65 occasionally showed other accompanying clinical features including abnormalities in tendon reflexes , involuntary movements , and reduced vibration sense . We also examined the frequency of the AD -SCA subtype , considering the effects of age at onset . In the 686 AD -SCA families , SCA 6 and Machado-Joseph disease /SCA 3 are frequent subtypes , followed by dentatorubral-pallidoluysian atrophy and 16 q-SCA . 16 q-SCA is not a rare subtype of Japanese AD -SCA , particularly in patients with ages at onset over 60 .