Severe Bleeding Diathesis in Siblings with Platelet Dysfunction due to a Novel Nonsense RASGRP2 Mutation

TH Open. 2020 Dec 25;4(4):e413-e416. doi: 10.1055/s-0040-1718910. eCollection 2020 Oct.

Abstract

Next-generation sequencing is increasingly applied during the diagnostic work-up of patients with bleeding diathesis and has facilitated the diagnosis of rare bleeding disorders such as inherited platelet function disorders. Mutations in RAS guanyl releasing protein 2 (RasGRP2), also known as calcium- and diacylglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), underlie a recently described platelet signal transduction abnormality. Here we present the case of a consanguineous family originating from Afghanistan with two siblings affected by recurrent severe mucocutaneous bleedings. Platelet function testing demonstrated a marked reduction of aggregation induced by collagen and adenosine diphosphate. Whole exome sequencing revealed a novel homozygous nonsense RASGRP2 mutation segregating with the bleeding disorder in the family.

Keywords: RASGRP2; bleeding diathesis; platelet dysfunction.

Publication types

  • Case Reports

Grants and funding

Funding This study was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation; grant 369799452/404459235) to M.L.K., Shenzhen Municipal Government of China (grant JCYJ20170817145536203) to M.F., and TÜFF-Gleichstellungsförderung to K.A. (grant 2563–0-0). Open access funding was provided by the publication fund of the TU Dresden.