Spectrum of the mutations in bernard-soulier syndrome

Anna Savoia, Shinji Kunishima, Daniela De Rocco, Barbara Zieger, Margaret L. Rand, Nuria Pujol-Moix, Umran Caliskan, Huseyin Tokgoz, Alessandro Pecci, Patrizia Noris, Alok Srivastava, Christopher Ward, Marie Christine Morel-Kopp, Marie Christine Alessi, Sylvia Bellucci, Philippe Beurrier, Emmanuel de Maistre, Rémi Favier, Nathalie Hézard, Marie Françoise Hurtaud-RouxVéronique Latger-Cannard, Cécile Lavenu-Bombled, Valérie Proulle, Sandrine Meunier, Claude Négrier, Alan Nurden, Hanitra Randrianaivo, Fabrizio Fabris, Helen Platokouki, Nurit Rosenberg, Basma Hadjkacem, Paula G. Heller, Mehran Karimi, Carlo L. Balduini, Annalisa Pastore, Francois Lanza

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1033-1045
Number of pages13
JournalHuman Mutation
Volume35
Issue number9
DOIs
Publication statusPublished - 2014

Keywords

  • Bernard-Soulier syndrome
  • GP1BA
  • GP1BB
  • GP9

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Medicine(all)

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  • Cite this

    Savoia, A., Kunishima, S., De Rocco, D., Zieger, B., Rand, M. L., Pujol-Moix, N., Caliskan, U., Tokgoz, H., Pecci, A., Noris, P., Srivastava, A., Ward, C., Morel-Kopp, M. C., Alessi, M. C., Bellucci, S., Beurrier, P., de Maistre, E., Favier, R., Hézard, N., ... Lanza, F. (2014). Spectrum of the mutations in bernard-soulier syndrome. Human Mutation, 35(9), 1033-1045. https://doi.org/10.1002/humu.22607