[Molecular genetic analysis of a Japanese family with Fabry disease]

A Japanese male patient with Fabry disease who had no activity of the lysosomal hydrolase alpha-galactosidase A (alpha-GalA) and female members of his family were analyzed. We cloned a cDNA encoded the mutant alpha-GalA, determined its nucleotide sequence, and found two nucleotide differences between the mutant and the wild-types cDNAs. The one difference, a C-to-T transition at nucleotide number 118, resulted in an amino acid substitution of Pro-40 by Ser. A transient expression assay demonstrated that this missense mutation was the cause of the deficiency of alpha-GalA activity in the patient. Gene analysis of the patient's family by PCR and subsequent sequencing demonstrated that all females were heterozygotes.