Novel Compound Heterozygous Mutations in Two Families With Bernard-Soulier Syndrome.

Background: Bernard-Soulier Syndrome (BSS) is a rare autosomal recessive bleeding disorder with large platelets and thrombocytopenia. It is caused by homozygous or compound heterozygous mutations in the GP1BA, GP1BB , or GP9 genes, which together encode the platelet surface receptor glycoprotein complex GPIb-IX-V. Objectives: We report two novel heterozygous mutations in the GP1BA and the GP9 genes, respectively. Patients/Methods: We analyzed the platelet glycoprotein expression by flow cytometry and screened the relevant genes for responsible mutations in two unrelated families. Results: Flow cytometric analyses revealed the absence of CD42a (GPIX) and CD42b (GPIb) on the platelets in the two affected siblings of family 1 and a significantly reduced expression of CD42b (GPIb) in the patient of family 2. In the two siblings, we identified a known frameshift (c.1601_1602delAT) and a novel nonsense mutation (c.1036C>T) in the GP1BA gene that abrogated the production of GP1bα. In the other patient, we found a novel missense mutation (c.112T>C) that was co-inherited with a common one (c.182A>G) in the GP9 gene, respectively. All analyzed heterozygous carriers were asymptomatic and had a normal GPIb-IX-V expression. Conclusions: The two novel GP1BA and GP9 mutations reported herein increment the number of causative genetic defects in BSS.
Competing Interests: PZ and OH, who are employed in Labdia GmbH, which is a 100% non-profit subsidiary of the Children's Cancer Research Institute (St. Anna Kinderkrebsforschung GmbH), have no commercial or financial relationships that could be construed as a potential conflict of interest. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Minkov, Zeitlhofer, Zoubek, Kager, Panzer and Haas.)