A missense mutation in the SOD1 gene in patients with amyotrophic lateral sclerosis from the Kii Peninsula and its vicinity, Japan

Unusually high incidences of amyotrophic lateral sclerosis (ALS) have been observed in the natives of the Kii Peninsula of Japan as well as the indigenous Chamorro people of Guam, Given the relatively high incidence of familial onset of the disease in the Kii Peninsula, we performed mutational analyses of the SOD1 gene of 23 patients (three familial cases and 20 sporadic cases) with ALS from the Kii Peninsula and its vicinity. In two of the 23 patients, we identified the same missense mutation (substitution of Thr for lie 113) in exon 4 as a heterozygous state. The Ile113Thr mutation in the SOD1 gene has been identified in some familial as well as sporadic cases with ALS, as a mutation with a low penetrance, This mutation has been reported to be associated with the formation of neurofibrillary tangles in an English family, which is a characteristic feature of ALS in the Kii Peninsula. These results suggest that the Ile113Thr mutation is a characteristic and relatively prevalent mutation in this area.