Spectrum of the Mutations in Bernard-Soulier Syndrome

Abstract

Bernard-Soulier syndrome (BSS) is a rare autosomal recessive bleeding disorder characterized by defects of the GPIb-IX-V complex, a platelet receptor for von Willebrand factor (VWF). Most of the mutations identified in the genes encoding for the GP1BA (GPIbα), GP1BB (GPIbβ), and GP9 (GPIX) subunits prevent expression of the complex at the platelet membrane or more rarely its interaction with VWF. As a consequence, platelets are unable to adhere to the vascular subendothelium and agglutinate in response to ristocetin. In order to collect information on BSS patients, we established an International Consortium for the study of BSS, allowing us to enrol and genotype 132 families (56 previously unreported). With 79 additional families for which molecular data were gleaned from the literature, the 211 families characterized so far have mutations in the GP1BA (28%), GP1BB (28%), or GP9 (44%) genes. There is a wide spectrum of mutations with 112 different variants, including 22 novel alterations. Consistent with the rarity of the disease, 85% of the probands carry homozygous mutations with evidence of founder effects in some geographical areas. This overview provides the first global picture of the molecular basis of BSS and will lead to improve patient diagnosis and management.Fil: Savoia, Anna. Università degli Studi di Trieste; Italia. Istituto di Ricovero e Cura a Carattere Scientifico “Burlo Garofolo”; ItaliaFil: Kunishima, Shinji. National Hospital Organization Nagoya Medical Center; JapónFil: De Rocco, Daniela. Università degli Studi di Trieste; ItaliaFil: Zieger, Barbara. University Medical Center of Freiburg; AlemaniaFil: Rand, Margaret L.. Hospital for Sick Children; CanadáFil: Pujol Moix, Nuria. Universidad de Barcelona; España. Sant Pau Research Institute; EspañaFil: Caliskan, Umran. Necmettin Erbakan University; TurquíaFil: Tokgoz, Huseyin. Necmettin Erbakan University; TurquíaFil: Pecci, Alessandro. University of Pavia; ItaliaFil: Noris, Patrizia. University of Pavia; ItaliaFil: Srivastava, Alok. Christian Medical College; IndiaFil: Ward, Christopher. University of Sydney; Australia. Royal North Shore Hospital; AustraliaFil: Morel Kopp, Marie Christine. University of Sydney; Australia. Royal North Shore Hospital; AustraliaFil: Alessi, Marie Christine. Université Aix Marseille; FranciaFil: Bellucci, Sylvia. Hôpital Lariboisière; FranciaFil: Beurrier, Philippe. Centre Hospitalier Universitaire d’Angers; FranciaFil: de Maistre, Emmanuel. Hôpital du Bocage; FranciaFil: Favier, Rémi. Hôpital d'enfants A Trousseau; FranciaFil: Hézard, Nathalie. Hôpital Robert Debré; FranciaFil: Hurtaud Roux, Marie Françoise. Hôpital Robert Debré; FranciaFil: Latger Cannard, Véronique. Centre de Compétence des Pathologies Plaquettaires Nord-Est; FranciaFil: Lavenu Bombled, Cécile. Universite Paris Sud; FranciaFil: Proulle, Valérie. Universite Paris Sud; FranciaFil: Meunier, Sandrine. Unité d’Hémostase Clinique de Lyon; FranciaFil: Négrier, Claude. Hôpital Edouard Herriot; FranciaFil: Nurden, Alan. Institut de Rythmologie et Modélisation Cardiaque; FranciaFil: Randrianaivo, Hanitra. Centre Hospitalier Universitaire, Saint-Pierre; FranciaFil: Fabris, Fabrizio. Università di Padova; ItaliaFil: Platokouki, Helen. Children's Hospital. Haemophilia Centre/Haemostasis Unit “Aghia Sophia”; GreciaFil: Rosenberg, Nurit. Sheba Medical Center. Amalia Biron Research Institute of Thrombosis and Hemostasis; IsraelFil: HadjKacem, Basma. Sfax University; TúnezFil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Karimi, Mehran. Shiraz University of Medical Sciences; IránFil: Balduini, Carlo L.. University of Pavia; ItaliaFil: Pastore, Annalisa. King's College London; Reino UnidoFil: Lanza, Francois. Université de Strasbourg; Franci