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

FEBS Lett. 1990 Jan 1;259(2):353-6. doi: 10.1016/0014-5793(90)80046-l.


We analyzed a male patient with Fabry's disease who had no activity of the lysosomal hydrolase alpha-galactosidase A (alpha-GalA) and female members of his family. We cloned a cDNA that encoded the mutant alpha-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 alpha-GalA activity in the patient. In vitro mutagenesis experiments demonstrated that Pro-40 is critical for the appearance of alpha-GalA activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Blotting, Northern
  • Cells, Cultured
  • DNA / genetics
  • Fabry Disease / enzymology*
  • Fabry Disease / genetics
  • Galactosidases / genetics*
  • Humans
  • Lysosomes / enzymology
  • Molecular Sequence Data
  • Mutation
  • Oligonucleotide Probes
  • Polymerase Chain Reaction
  • Proline*
  • Protein Conformation
  • Serine*
  • Skin / enzymology
  • alpha-Galactosidase / genetics*
  • alpha-Galactosidase / metabolism


  • Oligonucleotide Probes
  • Serine
  • DNA
  • Proline
  • Galactosidases
  • alpha-Galactosidase

Associated data

  • GENBANK/X16889