A case of Fabry's disease in a patient with no α‐galactosidase A activity caused by a single amino acid substitution of Pro‐40 by Ser

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Abstract
We analyzed a male patient with Fabry's disease who had no activity of the lysosomal hydrolase α‐galactosidase A (α‐GalA) and female members of his family. We cloned a cDNA that encoded the mutant α‐GalA, determined its nucleotide sequence, and found two nucleotide differences between the mutant and the wild‐type cDNAs. Although one difference was silent, the other 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 α‐GalA activity in the patient. In vitro mutagenesis experiments demonstrated that Pro‐40 is critical for the appearance ofa‐GalA activity.