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

• Published in: British journal of haematology Vol. 188; no. 6
• Main Authors: Ghalloussi, Dorsaf, Rousset‐rouvière, Caroline, Popovici, Cornel, Garaix, Florentine, Saut, Noémie, Saultier, Paul, Tsimaratos, Michel, Chambost, Hervé, Alessi, Marie-Christine, Baccini, Véronique
• Format: Journal Article
• Language: English
• Published: Wiley 19-02-2020
• Subjects: Human health and pathology; Life Sciences; platelet genetic diseases; platelet disorders; thrombocytopenia; platelet membrane; platelet aggregation
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.16374

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).