Bernard-Soulier Syndrome: Identification of a Novel GP1BB Variant in a Mauritanian Patient.

backgroundBernard-Soulier syndrome (BSS) is a rare bleeding disorder caused by defects in the GPIb-IX-V complex, which is essential for platelet adhesion. We report a novel case of BSS in a Mauritanian patient with a history of chronic bleeding since childhood, accompanied by thrombocytopenia and macroplatelets.

methodsDiagnosis was confirmed by flow cytometry and molecular analysis. The variant identified in the GP1BB gene (glycoprotein Ib platelet subunit beta, HGNC:4440, OMIM:138720; 22q11.21). The variant identified was annotated according to HGVS nomenclature.

resultsGenetic analysis identified a duplication of the GC dinucleotide in the GP1BB gene at genomic coordinates AF006988.1:g.13373_13374dupGC (transcript reference: NM_000407.4), resulting in a frameshift starting at amino acid residue 115 and generating a premature stop codon after 16 amino acids (p.Ala115Profs16). Flow cytometry demonstrated a significant reduction in GPIb and GPIX expression, explaining the platelet adhesion defect. Clinically, the patient's anemia worsened during adolescence with the onset of menstruation, requiring multiple transfusions that subsequently induced alloimmunization and transfusion incompatibility. Over an 18 years follow-up, the patient exhibited a persistent hemorrhagic syndrome and chronic iron-deficiency anemia, exacerbated by limited access to phenotyped blood in Mauritania. The variant alters the hydrophobicity and stability of the GPIbβ protein, impairing membrane integration and disrupting assembly of the GPIb-IX-V complex.

conclusionThis case highlights the importance of molecular diagnosis and genetic counseling in at-risk populations. In the absence of curative treatment, management relies on transfusions, antifibrinolytics, and avoidance of antiplatelet agents.