title: Novel genetic abnormalities in Bernard-Soulier syndrome in India.
abstract: Bernard-Soulier syndrome (BSS) is a severe inherited bleeding disorder due to defects in GPIb/IX/V, a platelet receptor that normally functions as a platelet membrane receptor for von Willebrand factor, thrombin and factor XI. BSS results from mutations in GP1BA, GP1BB or GP9 genes. In 15 patients with Bernard-Soulier syndrome from Western India, we amplified the entire coding sequences of GP1BA, GP1BB and GP9 genes and directly sequenced them. Twelve homozygous changes have been identified, out of which ten were novel mutations. These included eight frameshift mutations, i.e. p.Asp79GlufsX2, p.Phe314PhefsX37, p.Pro93ProfsX59, p.Asp89GlufsX63, p.Glu489AsnfsX64, p.Phe355PhefsX4, p.Leu479PhefsX19 and p.Leu531ArgfsX22, one missense mutation (p.Val262Gly) in GPIBA and one nonsense mutation (p.Tyr95X) in GP9. The two known changes include one missense mutation (p.Cys24Arg) in GP9 and one nonsense change (p.Trp46X) in GPIBB. A wide heterogeneity in the nature of mutations has been observed in Indian BSS patients in the present study. Identification of mutations in this rare platelet function disorder would pave way for genetic diagnosis in affected families in India, where consanguineous marriages are very common.
authors.affiliation: Department of Haemostasis and Thrombosis, National Institute of Immunohaematology, 13th Floor, KEM Hospital, Parel, Mumbai, 400012, Maharashtra, India.
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Ali
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.forename: Shrimati
authors.initials: S
authors.lastname: Shetty
mesh_terms: D000293:Adolescent; D001606:Bernard-Soulier Syndrome / Q000097:blood / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D006782:Hospitals, Special; D006801:Humans; D007194:India; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics*; D009154:Mutation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000032:analysis / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor; C032193:glycoprotein receptor GPIb-IX