title: 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.
authors.affiliation: Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy; Department of Medical Sciences, University of Trieste, Trieste, Italy.
authors.forename: Anna
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authors.lastname: Savoia
authors.forename: Shinji
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authors.lastname: Kunishima
authors.forename: Daniela
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authors.lastname: De Rocco
authors.forename: Barbara
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authors.lastname: Zieger
authors.forename: Margaret L
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authors.lastname: Rand
authors.forename: Nuria
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authors.lastname: Pujol-Moix
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authors.lastname: Caliskan
authors.forename: Huseyin
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authors.lastname: Tokgoz
authors.forename: Alessandro
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authors.forename: Patrizia
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authors.forename: Alok
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authors.forename: Christopher
authors.initials: C
authors.lastname: Ward
authors.forename: Marie-Christine
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authors.lastname: Morel-Kopp
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
authors.forename: Sylvia
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authors.lastname: Bellucci
authors.forename: Philippe
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authors.lastname: Beurrier
authors.forename: Emmanuel
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authors.lastname: de Maistre
authors.forename: Rémi
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authors.lastname: Favier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Hézard
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Hurtaud-Roux
authors.forename: Véronique
authors.initials: V
authors.lastname: Latger-Cannard
authors.forename: Cécile
authors.initials: C
authors.lastname: Lavenu-Bombled
authors.forename: Valérie
authors.initials: V
authors.lastname: Proulle
authors.forename: Sandrine
authors.initials: S
authors.lastname: Meunier
authors.forename: Claude
authors.initials: C
authors.lastname: Négrier
authors.forename: Alan
authors.initials: A
authors.lastname: Nurden
authors.forename: Hanitra
authors.initials: H
authors.lastname: Randrianaivo
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Fabris
authors.forename: Helen
authors.initials: H
authors.lastname: Platokouki
authors.forename: Nurit
authors.initials: N
authors.lastname: Rosenberg
authors.forename: Basma
authors.initials: B
authors.lastname: HadjKacem
authors.forename: Paula G
authors.initials: PG
authors.lastname: Heller
authors.forename: Mehran
authors.initials: M
authors.lastname: Karimi
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Balduini
authors.forename: Annalisa
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authors.lastname: Pastore
authors.forename: Francois
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authors.lastname: Lanza
mesh_terms: D000483:Alleles; D001606:Bernard-Soulier Syndrome / Q000175:diagnosis / Q000235:genetics*; D030561:Databases, Nucleic Acid; D018703:Founder Effect; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D064878:Web Browser; D014842:von Willebrand Diseases / Q000235:genetics
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor
keywords: Bernard-Soulier syndrome; GP1BA; GP1BB; GP9