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A GP1BA Variant in a Czech Family with Monoallelic Bernard-Soulier Syndrome

M. Skalníková, K. Staňo Kozubík, J. Trizuljak, Z. Vrzalová, L. Radová, K. Réblová, R. Holbová, T. Kurucová, H. Svozilová, J. Štika, I. Blaháková, B. Dvořáčková, M. Prudková, O. Stehlíková, M. Šmída, L. Křen, P. Smejkal, Š. Pospíšilová, M. Doubek

. 2022 ; 23 (2) : . [pub] 20220114

Language English Country Switzerland

Document type Case Reports, Journal Article

Persistent link   https://www.medvik.cz/link/bmc22011326

Grant support
MUNI/11/SUP/22/2020; MUNI/A/1595/2020 Masaryk University
NU20-08-00137 Ministry of Health of the Czech Republic
CZ.02.1.01/0.0/0.0/16_026/0008448 European Regional Development Fund-Project "A-C-G-T"
LM2018127, LM2018132 MEYS CR

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.

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