SCREENING AND DETECTION OF GENE-MUTATIONS IN JAPANESE PATIENTS WITH FABRY DISEASE BY NONRADIOACTIVE SINGLE-STRANDED CONFORMATION POLYMORPHISM ANALYSIS

We have applied non-radioactive polymerase chain reaction (PCR)-single -stranded conformation polymorphism (SSCP) to the detection of gene mu tations causing Fabry disease. Nineteen of 22 known mutations were det ected as electrophoretic mobility shifts on PCR-SSCP analysis. Then, D NA from newly diagnosed Japanese patients with the classical form of F abry disease was subjected to PCR-SSCP analysis, and 4 novel mutations (1 small deletion, 1 nonsense mutation and 2 missense mutations) and 1 neutral polymorphism were identified. Furthermore, identification of an asymptomatic heterozygote and a hemizygote with moderate clinical manifestations was successfully achieved by application of this method to a family with the variant form of Fabry disease. PCR-SSCP is usefu l for the gene diagnosis of etiologically heterogeneous Fabry disease. (C) 1997 Elsevier Science B.V.