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.

Center of Molecular Medicine Central European Institute of Technology Masaryk University 625 00 Brno Czech Republic

Department of Clinical Hematology University Hospital Brno and Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

Department of Internal Medicine Hematology and Oncology University Hospital Brno and Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

Department of Laboratory Methods Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

Department of Pathology University Hospital Brno and Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

Institute of Medical Genetics and Genomics University Hospital Brno and Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

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