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Bernard–Soulier syndrome: first human case due to a homozygous deletion of GP9 gene

Authors :
Florentine Garaix
Dorsaf Ghalloussi
Michel Tsimaratos
Caroline Rousset‐Rouvière
Noémie Saut
Marie-Christine Alessi
Hervé Chambost
Paul Saultier
Véronique Baccini
Cornel Popovici
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN)
Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Hôpital de la Timone [CHU - APHM] (TIMONE)
Laboratoire d'hématologie biologique [Hôpital de la Timone - Hôpital Nord - APHM]
Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)
Service de pédiatrie, d'hématologie et d'oncologie [Hôpital de La Timone - APHM]
Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)
Prémilleux, Annick
Source :
British Journal of Haematology, British Journal of Haematology, 2020, 188 (6), ⟨10.1111/bjh.16374⟩, British Journal of Haematology, Wiley, 2020, 188 (6), ⟨10.1111/bjh.16374⟩
Publication Year :
2020
Publisher :
Wiley, 2020.

Abstract

International audience; Bernard–Soulier Syndrome (BSS) is a rare (1:1 million) hereditary bleeding disorder caused by defects in the platelet glycoprotein (GP)‐Ib/IX/V complex, a receptor for von Willebrand factor (VWF) and thrombin (Lanza, 2006; Berndt & Andrews, 2011). Patients typically present with epistaxis, petechial or gingival bleeding with onset already in infancy. They present with macrothrombocytopenia and their platelets do not agglutinate in response to ristocetin, while maintaining a normal aggregation in response to a variety of aggregating agents. GPIb/IX/V complex consists of two GPIbα and four GPIbβ subunits stabilized by disulphide bonds (Luo et al., 2007). This heterodimer is non‐covalently associated with two GPIX and one GPV subunits. The N‐terminal residues of GPIbα form seven leucine‐rich repeats (LRRs) and include the binding sites for VWF and thrombin. BSS is due to biallelic loss‐of‐function pathogenic variants (deletions, insertions and nonsense mutations) in GPIBA, GPIBB or GP9 genes encoding GPIb/IX/V complex (Savoia et al., 2014). However, so far, no mutation in GP5 causing BSS has been reported yet. Most of the mutations prevent the formation of the complex or trafficking it through the endoplasmic reticulum and Golgi apparatus and alter receptor expression (Salles et al., 2008; Savoia et al., 2011; Nurden et al., 2012).

Details

ISSN :
13652141 and 00071048
Volume :
188
Database :
OpenAIRE
Journal :
British Journal of Haematology
Accession number :
edsair.doi.dedup.....8a6ed63ff2c126434d3515d1684a0828