Student Vilnius University Vilnius, Vilniaus Apskritis, Lithuania
Background: Bernard-Soulier Syndrome (BSS) is a rare platelet adhesion disorder, caused by a variant in one the genes coding for the GPIb-IX-V platelet surface receptor, classically following an autosomal recessive inheritance pattern. While biallelic patients display hemostatic deficiencies, monoallelic patients are usually asymptomatic. Herein, we detail a case of symptomatic autosomal dominant BSS caused by a rarely-encountered GP1BA variant.
Aims: To report a case of a rare monoallelic BSS variant in a female patient presenting with menorrhagia.
Methods: Detailed description of a clinical case.
Results: A 9-year-old female known for precocious puberty, menarche at the age of 9 and menorrhagia, leading to iron deficiency anemia (hemoglobin: 74 g/L), with ISTH Bleeding Assessment Tool (ISTH-BAT) score of 11, was consulted in our centre. Laboratory tests revealed normal platelet count with mean platelet volume at 10.9 fL; normal APTT, PT, fibrinogen tests; negative tests for von Willebrand disease; abnormal platelet function test (PFA-200); diminished response to low-dose ristocetin-induced aggregation, while platelet flow cytometry did not reveal characteristics typical of classic BSS. Next Generation Sequencing of blood DNA detected a heterozygous variant NM_000173.7:c.1036C>T, NP_000164.5:p.(Gln346Ter) in the GP1BA gene, which was not found in the gnomAD genomes and was classified as pathogenic by many in-silico predictors. During segregation analysis, identical variants were identified in the patient's mother, who had an ISTH-BAT of 8 and suffered from menorrhagia and persistent iron deficiency, and brother, who experienced several mild hemostatic challenges without any bleeding complications.
Conclusion(s): Even though BSS is an already established disease in its homozygous and compound heterozygous forms, only a handful of symptomatic monoallelic forms have been reported in literature. In patients with bleeding symptomatology and ambiguous platelet test results, novel and rare monoallelic forms, such as the one discussed in this report, should be suspected and further investigated.
