title: Bernard-Soulier syndrome: common ancestry in two African American families with the GP Ib alpha Leu129Pro mutation.
abstract: Bernard-Soulier syndrome (BSs) is a rare bleeding disorder characterized by circulating giant platelets, thrombocytopenia, and a prolonged bleeding time. BSs usually has an autosomal recessive inheritance pattern, with a preponderance of Caucasian and Japanese ancestry when the ethnic background has been reported. Underlying this disorder of platelet function is a defect in the platelet glycoprotein (GP) Ib-IX-V complex, composed of four polypeptides, 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 study, 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 mutation, 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 BSs 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.
authors.affiliation: Department of Medicine, Christiana Care Health System, Wilmington, Delaware, USA.
authors.forename: J V
authors.initials: JV
authors.lastname: Antonucci
authors.forename: E S
authors.initials: ES
authors.lastname: Martin
authors.forename: P J
authors.initials: PJ
authors.lastname: Hulick
authors.forename: A
authors.initials: A
authors.lastname: Joseph
authors.forename: S E
authors.initials: SE
authors.lastname: Martin
mesh_terms: D000349:Africa / Q000208:ethnology; D001606:Bernard-Soulier Syndrome / Q000235:genetics*; D044383:Black People / Q000235:genetics; D002886:Chromosomes, Human, Pair 17; D016384:Consensus Sequence; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006720:Homozygote; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D014481:United States; D001741:Black or African American
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex