Spectrum of the Mutations in Bernard-Soulier Syndrome
Por:
Savoia, A, Kunishima, S, De Rocco, D, Zieger, B, Rand, ML, Pujol-Moix, N, Caliskan, U, Tokgoz, H, Pecci, A, Noris, P, Srivastava, A, Ward, C, Morel-Kopp, MC, Alessi, MC, Bellucci, S, Beurrier, P, de Maistre, E, Favier, R, Hezard, N, Hurtaud-Roux, MF, Latger-Cannard, V, Lavenu-Bombled, C, Proulle, V, Meunier, S, Negrier, C, Nurden, A, Randrianaivo, H, Fabris, F, Platokouki, H, Rosenberg, N, HadjKacem, B, Heller, PG, Karimi, M, Balduini, CL, Pastore, A, Lanza, F
Publicada:
1 sep 2014
Resumen:
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 (GPIb alpha), GP1BB (GPIb beta), 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. (C) 2014 Wiley Periodicals, Inc.
Filiaciones:
Savoia, A:
Inst Maternal & Child Hlth IRCCS Burlo Garofolo, Trieste, Italy
Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy
Kunishima, S:
Natl Hosp Org Nagoya Med Ctr, Clin Res Ctr, Dept Adv Diag, Nagoya, Aichi, Japan
De Rocco, D:
Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy
Zieger, B:
Univ Med Ctr Freiburg, Dept Pediat & Adolescent Med, Freiburg, Germany
Rand, ML:
Hosp Sick Children, Dept Paediat, Div Haematol Oncol, Toronto, ON M5G 1X8, Canada
Pujol-Moix, N:
Autonomous Univ Barcelona, Dept Med, Barcelona, Spain
St Pau Res Inst, Barcelona, Spain
Caliskan, U:
Necmettin Erbakan Univ, Meram Fac Med, Meram Konya, Turkey
Tokgoz, H:
Necmettin Erbakan Univ, Meram Fac Med, Meram Konya, Turkey
Pecci, A:
Univ Pavia, IRCCS Policlin San Matteo Fdn, I-27100 Pavia, Italy
Noris, P:
Univ Pavia, IRCCS Policlin San Matteo Fdn, I-27100 Pavia, Italy
Srivastava, A:
Christian Med Coll & Hosp, Dept Haematol, Vellore, Tamil Nadu, India
Ward, C:
Univ Sydney, Kolling Inst Med Res, Northern Blood Res Ctr, St Leonards, NSW, Australia
Royal N Shore Hosp, Dept Hematol & Transfus Med, St Leonards, NSW 2065, Australia
Morel-Kopp, MC:
Univ Sydney, Kolling Inst Med Res, Northern Blood Res Ctr, St Leonards, NSW, Australia
Royal N Shore Hosp, Dept Hematol & Transfus Med, St Leonards, NSW 2065, Australia
Alessi, MC:
Univ Aix Marseille, Fac Med, INSERM UMR 1062, Lab Hematol, Marseille, France
Bellucci, S:
Hop Lariboisiere, AP HP, Serv Hematol Biol, F-75475 Paris, France
Beurrier, P:
Ctr Hosp Univ Angers, Ctr Traitement Hemophilie, Angers, France
de Maistre, E:
CHU Dijon, CRTH, Dijon, France
Hop Bocage, Ctr Coagulopathies, Dijon, France
Favier, R:
Hop Enfants Trousseau, Assistance Publ Hop Paris, Serv Hematol Biol, InsermU1009, Villejuif, France
Hezard, N:
CHU Reims, Hop Robert Debre, Lab Hematol, Reims, France
Hurtaud-Roux, MF:
Hop Robert Debre, Serv Hematol Biol, F-75019 Paris, France
Latger-Cannard, V:
CHU, Serv Hematol Biol, Nancy, France
Ctr Competence Pathol Plaquettaires Nord Est, Pessac, France
Lavenu-Bombled, C:
Univ Paris Sud, Hop Bicetre, Assistance Publ Hop Paris, Serv Hematol Biol,CRPP, F-94275 Le Kremlin Bicetre, France
Proulle, V:
Univ Paris Sud, Hop Bicetre, Assistance Publ Hop Paris, Serv Hematol Biol,CRPP, F-94275 Le Kremlin Bicetre, France
Meunier, S:
CHU Lyon, Unite Hemostase Clin, Lyon, France
Negrier, C:
Hop Edouard Herriot, Unite Hemostase Clin, Lyon, France
Nurden, A:
Hop Xavier Arnozan, Inst Rythmol & Modelisat Cardiaque LIRYC Platefor, Pessac, France
Randrianaivo, H:
Ctr Hosp Univ, Pole Femme Mere Enfant, Med Genet Unit, St Pierre, Reunion, France
Fabris, F:
Univ Padua, Dept Med DIMED, Padua, Italy
Platokouki, H:
Childrens Hosp, Haemostasis Unit Aghia Sophia, Haemophilia Ctr, Athens, Greece
Rosenberg, N:
Chaim Sheba Med Ctr, Amalia Biron Res Inst Thrombosis & Hemostasis, Tel Hashomer, Israel
HadjKacem, B:
Sfax Univ, Ctr Biotechnol Sfax, Sfax, Tunisia
Heller, PG:
Univ Buenos Aires, CONICET, Inst Invest Med A Lanari, Buenos Aires, DF, Argentina
Karimi, M:
Shiraz Univ Med Sci, Hematol Res Ctr, Shiraz, Iran
Balduini, CL:
Univ Pavia, IRCCS Policlin San Matteo Fdn, I-27100 Pavia, Italy
Pastore, A:
Kings Coll London, Dept Clin Neurosci, London WC2R 2LS, England
Lanza, F:
Ctr Competence Pathol Plaquettaires Nord Est, Pessac, France
INSERM UMR S 949, Strasbourg, France
EFS Alsace, Strasbourg, France
Univ Strasbourg, Strasbourg, France
Open Access
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