Alpha-galactosidase gene mutations in Fabry disease: heterogeneous expressions of mutant enzyme proteins

Hum Genet. 1995 May;95(5):557-61. doi: 10.1007/BF00223869.

Abstract

Five point mutations were identified in unrelated Japanese Fabry disease hemizygotes: three new missense mutations, C142Y (425 G-->A), A156V (467 C-->T), and L166V (496 C-->G) in exon 3; one new splice site mutation at the 3' end of the consensus sequence in exon 4; one previously reported nonsense mutation, W44X (131 G-->A). C142Y expressed 50% of the normal enzyme protein in COS-1 cells, but catalytic activity was not detected. Both A156V and L166V expressed significant amounts of residual enzyme activity (6.7% and 9.8%) and enzyme proteins (10% each), the latter were more thermolabile at neutral pH than at acid pH, in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Cell Line, Transformed
  • Child
  • Child, Preschool
  • DNA / analysis
  • DNA / chemistry
  • DNA Primers / chemistry
  • Enzyme Stability
  • Exons
  • Fabry Disease / enzymology*
  • Fabry Disease / genetics*
  • Gene Expression Regulation, Enzymologic*
  • Hot Temperature
  • Humans
  • Hydrogen-Ion Concentration
  • Japan
  • Male
  • Molecular Sequence Data
  • Point Mutation*
  • alpha-Galactosidase / chemistry
  • alpha-Galactosidase / genetics*

Substances

  • DNA Primers
  • DNA
  • alpha-Galactosidase