Spectrum of the Mutations in Bernard-Soulier Syndrome

被引：110

作者：

Savoia, Anna ^{[1
,2
]}

Kunishima, Shinji ^{[3
]}

De Rocco, Daniela ^{[2
]}

Zieger, Barbara ^{[4
]}

Rand, Margaret L. ^{[5
]}

Pujol-Moix, Nuria ^{[6
,7
]}

Caliskan, Umran ^{[8
]}

Tokgoz, Huseyin ^{[8
]}

Pecci, Alessandro ^{[9
]}

Noris, Patrizia ^{[9
]}

Srivastava, Alok ^{[10
]}

Ward, Christopher ^{[11
,12
]}

Morel-Kopp, Marie-Christine ^{[11
,12
]}

Alessi, Marie-Christine ^{[13
]}

Bellucci, Sylvia ^{[14
]}

Beurrier, Philippe ^{[15
]}

de Maistre, Emmanuel ^{[16
,17
]}

Favier, Remi ^{[18
]}

Hezard, Nathalie ^{[19
]}

Hurtaud-Roux, Marie-Francoise ^{[20
]}

Latger-Cannard, Veronique ^{[21
,22
]}

Lavenu-Bombled, Cecile ^{[23
]}

Proulle, Valerie ^{[23
]}

Meunier, Sandrine ^{[24
]}

Negrier, Claude ^{[25
]}

Nurden, Alan ^{[26
]}

Randrianaivo, Hanitra ^{[27
]}

Fabris, Fabrizio ^{[28
]}

Platokouki, Helen ^{[29
]}

Rosenberg, Nurit ^{[30
]}

HadjKacem, Basma ^{[31
]}

Heller, Paula G. ^{[32
]}

Karimi, Mehran ^{[33
]}

Balduini, Carlo L. ^{[9
]}

Pastore, Annalisa ^{[34
]}

Lanza, Francois ^{[22
,35
,36
,37
]}

机构：

[1] Inst Maternal & Child Hlth IRCCS Burlo Garofolo, Trieste, Italy

[2] Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy

[3] Natl Hosp Org Nagoya Med Ctr, Clin Res Ctr, Dept Adv Diag, Nagoya, Aichi, Japan

[4] Univ Med Ctr Freiburg, Dept Pediat & Adolescent Med, Freiburg, Germany

[5] Hosp Sick Children, Dept Paediat, Div Haematol Oncol, Toronto, ON M5G 1X8, Canada

[6] Autonomous Univ Barcelona, Dept Med, Barcelona, Spain

[7] St Pau Res Inst, Barcelona, Spain

[8] Necmettin Erbakan Univ, Meram Fac Med, Meram Konya, Turkey

[9] Univ Pavia, IRCCS Policlin San Matteo Fdn, I-27100 Pavia, Italy

[10] Christian Med Coll & Hosp, Dept Haematol, Vellore, Tamil Nadu, India

[11] Univ Sydney, Kolling Inst Med Res, Northern Blood Res Ctr, St Leonards, NSW, Australia

[12] Royal N Shore Hosp, Dept Hematol & Transfus Med, St Leonards, NSW 2065, Australia

[13] Univ Aix Marseille, Fac Med, INSERM UMR 1062, Lab Hematol, Marseille, France

[14] Hop Lariboisiere, AP HP, Serv Hematol Biol, F-75475 Paris, France

[15] Ctr Hosp Univ Angers, Ctr Traitement Hemophilie, Angers, France

[16] CHU Dijon, CRTH, Dijon, France

[17] Hop Bocage, Ctr Coagulopathies, Dijon, France

[18] Hop Enfants Trousseau, Assistance Publ Hop Paris, Serv Hematol Biol, InsermU1009, Villejuif, France

[19] CHU Reims, Hop Robert Debre, Lab Hematol, Reims, France

[20] Hop Robert Debre, Serv Hematol Biol, F-75019 Paris, France

[21] CHU, Serv Hematol Biol, Nancy, France

[22] Ctr Competence Pathol Plaquettaires Nord Est, Pessac, France

[23] Univ Paris Sud, Hop Bicetre, Assistance Publ Hop Paris, Serv Hematol Biol,CRPP, F-94275 Le Kremlin Bicetre, France

[24] CHU Lyon, Unite Hemostase Clin, Lyon, France

[25] Hop Edouard Herriot, Unite Hemostase Clin, Lyon, France

[26] Hop Xavier Arnozan, Inst Rythmol & Modelisat Cardiaque LIRYC Platefor, Pessac, France

[27] Ctr Hosp Univ, Pole Femme Mere Enfant, Med Genet Unit, St Pierre, Reunion, France

[28] Univ Padua, Dept Med DIMED, Padua, Italy

[29] Childrens Hosp, Haemostasis Unit Aghia Sophia, Haemophilia Ctr, Athens, Greece

[30] Chaim Sheba Med Ctr, Amalia Biron Res Inst Thrombosis & Hemostasis, Tel Hashomer, Israel

[31] Sfax Univ, Ctr Biotechnol Sfax, Sfax, Tunisia

[32] Univ Buenos Aires, CONICET, Inst Invest Med A Lanari, Buenos Aires, DF, Argentina

[33] Shiraz Univ Med Sci, Hematol Res Ctr, Shiraz, Iran

[34] Kings Coll London, Dept Clin Neurosci, London WC2R 2LS, England

[35] INSERM UMR S 949, Strasbourg, France

[36] EFS Alsace, Strasbourg, France

[37] Univ Strasbourg, Strasbourg, France

来源：

HUMAN MUTATION | 2014年 / 35卷 / 09期

关键词：

Bernard-Soulier syndrome; GP1BA; GP1BB; GP9; GLYCOPROTEIN-IB-ALPHA; LEUCINE-RICH REPEAT; VON-WILLEBRAND DISEASE; BASE-PAIR DELETION; IDIOPATHIC THROMBOCYTOPENIC PURPURA; HETEROZYGOUS MISSENSE MUTATION; SEVERE BLEEDING TENDENCY; SYNDROME TYPE BOLZANO; GPIB-IX COMPLEX; BETA-GENE;

D O I：

10.1002/humu.22607

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1033 / 1045

页数：13

共 123 条

[91] Phosphatidylserine exposure and other apoptotic-like events in Bernard-Soulier syndrome platelets [J].