Clinical features and diagnosis by recombinant DNA techniques of familial amyloid polyneuropathy in Japan.

Diagnosis of familial amyloid polyneuropathy (FAP) was investigated by recombinant DNA techniques using Southern blot hybridization in 49 constituents of FAP pedigrees originated from Nagano and Hiroshima Prefectures in Japan. The results were correlated with clinical features of the patients. Twenty-nine patients originated from Ogawa Village in Nagano Prefecture of the central part of Japan had typical clinical features of Andrade type FAP including polyneuropathy with autonomic disorders. The variant prealbumin gene with a substitution of methionine (Met) for valine (Val) at position 30 was detected in their DNA analysis (positive DNA diagnosis). In 5 cases from Nagano and Hiroshima Prefectures who had clinical features of Andrade type FAP but no family history, DNA diagnosis was positive. In another 5 members of FAP pedigrees originated from Ogawa Village without clinical features of FAP, DNA diagnosis was positive. Two cases originated from Iiyama City in Nagano, who had central nervous system disorders resembling spinocerebellar degeneration with spastic paraplegia besides clinical features of Andrade type FAP, had the Val-Met interchange variant prealbumin gene. In a case from the same Iiyama family who had only the central nervous system disorders without clinical features of FAP, DNA diagnosis was negative. These findings indicate that the presence of the variant prealbumin gene closely linked to the clinical manifestations of Andrade type FAP. The diagnostic DNA analysis was considered to be useful for the diagnosis of Andrade type FAP for sporadic cases as well as so far nonsymptomatic gene carriers. In conclusion, FAP patients originated from Iiyama City and Ogawa village were considered to have the same mutation despite the variances in clinical features.