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.
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.
Koide
T
T
Department of Cell Biology, National Institute for Basic Biology, Aichi, Japan.
Ishiura
M
M
Iwai
K
K
Inoue
M
M
Kaneda
Y
Y
Okada
Y
Y
Uchida
T
T
D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D000795:Fabry Disease / Q000201:enzymology* / Q000235:genetics; D005696:Galactosidases / Q000235:genetics*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011392:Proline; D011487:Protein Conformation; D012694:Serine; D012867:Skin / Q000201:enzymology; D000519:alpha-Galactosidase / Q000235:genetics* / Q000378:metabolism
D015345:Oligonucleotide Probes; D012694:Serine; D004247:DNA; D011392:Proline; D005696:Galactosidases; D000519:alpha-Galactosidase