?-Galactosidase gene mutations in Fabry disease: heterogeneous expressions of mutant enzyme proteins

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.