Bernard-Soulier syndrome: Common ancestry in two African American families with the GP Ib? 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.

Occurrence of the Asn45Ser mutation in the GPIX gene in a Belgian patient with Bernard Soulier syndrome

“…Most of the mutations have been identified in the GPIba gene. [14][15][16][17][18][19] But mutations were also found in GPIbb [20][21][22][23][24][25] and GPIX. [26][27][28][29][30][31][32][33][34] We here report on the characterization of an Asn45Ser mutation in the GPIX gene of a Belgian Bernard Soulier patient.…”

Mutations in human glycine N-methyltransferase give insights into its role in methionine metabolism

“…6A), one might expect that the change of this residue to proline would have a major effect on the conformation and stability of this helix. A change of leucine to proline is a very common cause of human metabolic abnormalities, occurring, for example, in autosomal dominant long QT syndrome (Antonucci et al 2000) and Bernard-Soulier syndrome (Krahn et al 2000).…”

A Case Report of Bernard-Soulier Syndrome in Differential Diagnosis of Immune Thrombocytopenic Purpura.

“…†Originally reported as codon 126. [31] Female [32] 14 years old Male [33] Angiodysplasia + breast cancer + Hepatitis C 48 years old Female [34] Tuberculosis 14 years old Female [35] Hepatitis 42 years old Female [36] Coronary artery disease 68 years old Male [37] Atherosclerosis and unstable angina 66 years old Male [38] Pregnancy Variable Female [39] Aquagenicurticarial 18 years old Male [45] Developmental dysplasia of her left hip (DDH) 40 years old Female [46] Acute myeloid leukemia 21 years old Female [25] Myocardial infarction 60 and 64 years old Male [26] [63] 3233-3236delTGAG Premature termination [64] 3285C>T Leu57Phe [65] 3309T>C Cys65Arg [66] 3343delT Premature termination [67] 3502T>C Leu129Pro [68][69] 3583C>T Ala156Val [70-71-72] 3621-3656del Premature termination [72] 3651-3653delCTC del Leu179 [73] 3741T>A Cys209Ser [74][75] 3998-3999delTG Premature termination [12] 4145G>A Trp343stop [76] 4444insT Premature termination [12-14-75] 4447C>A Ser444stop [13] 4464delA Premature termination [12][13][14] 4591-4592delAt Premature termination [77-78-79] 4610G>A Trp498stop [66][67][68][69][70][71][72][73]…”