A novel germline mutation in GP1BA gene N-terminal domain in monoallelic Bernard-Soulier syndrome. (17th November 2018)

• Record Type: Journal Article
• Authors: Trizuljak, Jakub; Kozubík, Kateřina Staňo; Radová, Lenka; Pešová, Michaela; Pál, Karol; Réblová, Kamila; Stehlíková, Olga; Smejkal, Petr; Zavřelová, Jiřina; Pacejka, Milan; Mayer, Jiří; Pospíšilová, Šárka; Doubek, Michael
• Is Part Of: Platelets. Volume 29:Number 8(2018)
• Page Start: 827
• Page End: 833
• Publication Date: 2018-11-17
• Subjects: Autosomal dominant variant -- GP1BA -- Inherited thrombocytopenia -- monoallelic Bernard-Soulier syndrome; Blood platelets -- Periodicals; Blood Platelets -- Periodicals; 615.39
• DOI: 10.1080/09537104.2018.1529300
• Languages: English
• ISSNs: 0953-7104

Abstract

Abstract: Mutations in the GP1BA gene have been associated with platelet-type von Willebrand disease and Bernard-Soulier syndrome. Here, we report a novel GP1BA mutation in a family with autosomal dominant macrothrombocytopenia and mild bleeding. We performed analyses of seven family members. Using whole-exome sequencing of germline DNA samples, we identified a heterozygous single-nucleotide change in GP1BA (exone2:c.176T>G), encoding a p.Leu59Arg substitution in the N-terminal domain, segregating with macrothrombocytopenia. This variant has not been previously reported. We also analysed the structure of the detected sequence variant in silico . In particular, we used the crystal structure of the human platelet receptor GP Ibα N-terminal domain. Replacement of aliphatic amino-acid Leu 59 with charged, polar and larger arginine probably disrupts the protein structure. An autosomal dominant mode of inheritance, a family history of mild bleeding episodes, aggregation pattern in affected individuals together with evidence of mutation occurring in part of the GP1BA gene encoding the leucine-rich repeat region suggest a novel variant causing monoallelic Bernard-Soulier syndrome.