TY - JOUR
T1 - Spectrum of the mutations in bernard-soulier syndrome
AU - Savoia, Anna
AU - Kunishima, Shinji
AU - De Rocco, Daniela
AU - Zieger, Barbara
AU - Rand, Margaret L.
AU - Pujol-Moix, Nuria
AU - Caliskan, Umran
AU - Tokgoz, Huseyin
AU - Pecci, Alessandro
AU - Noris, Patrizia
AU - Srivastava, Alok
AU - Ward, Christopher
AU - Morel-Kopp, Marie Christine
AU - Alessi, Marie Christine
AU - Bellucci, Sylvia
AU - Beurrier, Philippe
AU - de Maistre, Emmanuel
AU - Favier, Rémi
AU - Hézard, Nathalie
AU - Hurtaud-Roux, Marie Françoise
AU - Latger-Cannard, Véronique
AU - Lavenu-Bombled, Cécile
AU - Proulle, Valérie
AU - Meunier, Sandrine
AU - Négrier, Claude
AU - Nurden, Alan
AU - Randrianaivo, Hanitra
AU - Fabris, Fabrizio
AU - Platokouki, Helen
AU - Rosenberg, Nurit
AU - Hadjkacem, Basma
AU - Heller, Paula G.
AU - Karimi, Mehran
AU - Balduini, Carlo L.
AU - Pastore, Annalisa
AU - Lanza, Francois
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Bernard-Soulier syndrome
KW - GP1BA
KW - GP1BB
KW - GP9
UR - http://www.scopus.com/inward/record.url?scp=84906056536&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906056536&partnerID=8YFLogxK
U2 - 10.1002/humu.22607
DO - 10.1002/humu.22607
M3 - Article
C2 - 24934643
AN - SCOPUS:84906056536
VL - 35
SP - 1033
EP - 1045
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 9
ER -