1. A GP1BA Variant in a Czech Family with Monoallelic Bernard-Soulier Syndrome
- Author
-
Magdalena Skalníková, Kateřina Staňo Kozubík, Jakub Trizuljak, Zuzana Vrzalová, Lenka Radová, Kamila Réblová, Radka Holbová, Terézia Kurucová, Hana Svozilová, Jiří Štika, Ivona Blaháková, Barbara Dvořáčková, Marie Prudková, Olga Stehlíková, Michal Šmída, Leoš Křen, Petr Smejkal, Šárka Pospíšilová, and Michael Doubek
- Subjects
Blood Platelets ,Male ,GP1BA ,QH301-705.5 ,DNA Mutational Analysis ,Catalysis ,Immunophenotyping ,Inorganic Chemistry ,autosomal dominant ,monoallelic ,macrothrombocytopenia ,Humans ,Genetic Predisposition to Disease ,Physical and Theoretical Chemistry ,Biology (General) ,Molecular Biology ,QD1-999 ,Spectroscopy ,Alleles ,Genetic Association Studies ,Czech Republic ,Platelet Count ,Brief Report ,Organic Chemistry ,Genetic Variation ,General Medicine ,Thrombocytopenia ,Bernard-Soulier syndrome ,Computer Science Applications ,Pedigree ,Chemistry ,Phenotype ,Platelet Glycoprotein GPIb-IX Complex ,Female - Abstract
Bernard-Soulier syndrome (BSS) is a rare inherited disorder characterized by unusually large platelets, low platelet count, and prolonged bleeding time. BSS is usually inherited in an autosomal recessive (AR) mode of inheritance due to a deficiency of the GPIb-IX-V complex also known as the von Willebrand factor (VWF) receptor. We investigated a family with macrothrombocytopenia, a mild bleeding tendency, slightly lowered platelet aggregation tests, and suspected autosomal dominant (AD) inheritance. We have detected a heterozygous GP1BA likely pathogenic variant, causing monoallelic BSS. A germline GP1BA gene variant (NM_000173:c.98G > A:p.C33Y), segregating with the macrothrombocytopenia, was detected by whole-exome sequencing. In silico analysis of the protein structure of the novel GPIbα variant revealed a potential structural defect, which could impact proper protein folding and subsequent binding to VWF. Flow cytometry, immunoblot, and electron microscopy demonstrated further differences between p.C33Y GP1BA carriers and healthy controls. Here, we provide a detailed insight into its clinical presentation and phenotype. Moreover, the here described case first presents an mBSS patient with two previous ischemic strokes.
- Published
- 2022