The multiple cases of Fabry disease in a Russian family caused by an E341Kamino acid substitution in the alpha-galactosidase A

A large Russian family with multiple cases of Fabry disease in several gene rations is presented. Fourteen family members were clinico-biochemically ex amined. Among 12 adult children (19-32 years old) of one couple, five sons manifested angiokeratotic skin lesions and other Fabry symptoms. Biochemica l studies including an enzyme assay, the analysis of glycosphingolipid excr etion and isoelectric focusing of a patient leukocyte extract allowed us to identify Fabry disease in four affected brothers and to establish the hete rozygous status of their mother. The analysis of genomic DNA of four patien ts and their mother revealed a novel E341K missense mutation caused by a G to A transition (codon 341 GAA-AAA) in the alpha-galactosidase A gene. (C) 1999 Elsevier Science B.V. All rights reserved.