IDENTIFICATION OF A NOVEL POINT MUTATION (S65T) IN ALPHA-GALACTOSIDASE-A GENE IN CHINESE PATIENTS WITH FABRY-DISEASE

Fabry disease is an X-linked inborn error of sphingolipid catabolism r esulting from deficient enzyme activity of alpha-galactosidase A. The molecular defects of human alpha-galactosidase A gene causing Fabry di sease have been characterized, including gene rearrangement and point mutations, which show the genetic heterogeneity in Fabry disease. To c haracterize the molecular defects of these patients, each exon of alph a-galactosidase A gene including intron-exon junctions were PCR amplif ied using biotin-labelled primer and sequenced using magnetic beads so lid phase sequencing. A G to C transversion was identified in the last nucleotide of exon 1 in two unrelated Chinese patients. This mutation obliterates an EcoN1 restriction site. Family studies show close link age with the affected family members. Screening of 100 alleles (22 mal es, 39 females) of unrelated normal Chinese can not find this mutation . This mutation not only changes the amino acid from serine to threoni ne, but also likely cause splicing defects. To our knowledge, this is the first report of mutation in Chinese patients with Fabry disease, a nd a novel mutation causing Fabry disease not reported in literature p reviously. (C) 1998 Wiley-Liss, Inc.