Identification of the gene for hereditary spinocerebellar degeneration and its usage for diagnosis.

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The dominantly inherited spinocerebellar ataxias are a cluster of genetically heterogeneous neuro-degenerative disorders. More than 500 people living in Hokkaido are affected with these diseases. Recent advances in molecular genetics have led to the identification of 7 loci named as SCAl to SCA7.Among them, abnormal expansions of the CAG trinucleotide repeat have been identified in the patients with SCAl, SCA2 and SCA3. Although number of patients exceeds 30 % in Japanese ataxic patients, the location and specific abnormalities of the gene for Holmes' ataxia were unknown when we started this research. Through two years research, we have clarified following evidences ;1) The responsible gene for the half of the patients with Holiness' ataxia in the Japanese are identical to that of SCA6.2) The responsible gene for SCA6 is a gene for alphalA - voltage dependent calcium channel (CACNL1A4) mapped at 19p13.3) An abnormal expansions of the CAG trinucleotide repeat located in the CACNL1A4 was observed in the patients with SCA6.4) The number of CAG repeat inversely correlated with age of onset.5) Strong linkage disequilibrium suggested that SCA6 in the Japanese in Hokkaido may derive from a single common ancestry.It should be solved in a future that why and how expanded CAG repeat, which translated into poly glutamine chain, causes a selective neuronal cell death.