[Spinocerebellar ataxia: advances in genetic research and its clinical implication]

Hereditary spinocerebellar ataxia (SCA) is a cluster of genetically heterogeneous disorders, and was classified based on the mode of inheritance and clinicopathological features. Recent molecular genetic studies determined the locus of responsible mutation in 7 dominant SCAs ¿SCA1, SCA2, Machado-Joseph disease (SCA3), SCA4, SCA5, SCA7, DRPLA¿ and one recessive SCA ¿Friedreich's ataxia (FRDA)¿. Of these disorders, abnormal CAG repeat expansions were identified in the mutation of 5 dominant SCAs (SCA1, SCA2, MJD, DRPLA), and abnormal GAA repeat expansion in FRDA mutation. Thus, all these SCAs are members of "triplet repeat disorders". As found in other triplet repeat disorders, number of triplet repeat correlates with clinical severity and variety of clinical phenotypes: age at onset is inversely correlated with repeat length. Throughout the study for SCA gene mutation, we found SCA1, SCA2, and MJD in Hokkaido. More than half were MJD in our subjects, indicating that this disorder is the most prevalent in the dominant SCA seen in Hokkaido. The results of this molecular genetic study and their implication for understanding the variety of SCA phenotype are presented in this symposium.