Bernard-Soulier syndrome: Common ancestry in two African American familieswith the GP Ib alpha Leu129Pro mutation

Bernard-Soulier syndrome (BSs) is a rare bleeding disorder characterized by circulating giant platelets, thrombocytopenia, and a prolonged bleeding ti me. BSs usually has an autosomal recessive inheritance pattern, with a prep onderance of Caucasian and Japanese ancestry when the ethnic background has been reported. Underlying this disorder of platelet function is a defect i n the platelet glycoprotein (GP) Ib-IX-V complex, composed of four polypept ides, GP Ib alpha, GP Ib beta, GP IX, and GP V. Molecular characterization of individuals with BSs has identified mutations in the GP Ib alpha, GP Ib beta, and GP IX genes responsible for the expressed phenotype, In this stud y, we report a family of African-American descent, with autosomal recessive BSs showing a point mutation in codon 129 of the GP Ib alpha gene. This mu tation, CTC:wild-type to CCC:mutant, is similar to that of another African American family where the resulting leucine to proline substitution in the 5(th) leucine-rich repeat of GP Ib alpha is responsible for the observed BS s phenotype, Comparison of the intragenic polymorphisms of GP Ib alpha, as well as microsatellite markers in a 17.5 cM region of chromosome 17p12 that contains the GP Ib alpha gene, suggests that, although socially unrelated, the Leu129Pro mutation in these two families has a common founder. (C) 200 0 Wiley-Liss, Inc.