Novel variants in FERMT3 and RASGRP2-Genetic linkage in Glanzmann-like bleeding disorders

Pediatr Blood Cancer. 2020 Feb;67(2):e28078. doi: 10.1002/pbc.28078. Epub 2019 Nov 14.

Abstract

Defects of platelet intracellular signaling can result in severe platelet dysfunction. Several mutations in each of the linked genes FERMT3 and RASGRP2 on chromosome 11 causing a Glanzmann-like bleeding phenotype have been identified so far. We report on novel variants in two unrelated pediatric patients with severe bleeding diathesis-one with leukocyte adhesion deficiency type III due to a homozygous frameshift in FERMT3 and the other with homozygous variants in both, FERMT3 and RASGRP2. We focus on the challenging genetic and functional variant assessment and aim to accentuate the risk of obtaining misleading results due to the phenomenon of genetic linkage.

Keywords: bleeding disorders other than hemophilia; hematology; hemostasis and thrombosis; platelet disorders.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Blood Platelet Disorders / genetics
  • Blood Platelet Disorders / pathology*
  • Child
  • Female
  • Genetic Linkage
  • Guanine Nucleotide Exchange Factors / genetics*
  • Hemorrhagic Disorders / genetics
  • Hemorrhagic Disorders / pathology*
  • Homozygote
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Pedigree
  • Phenotype
  • Prognosis

Substances

  • FERMT3 protein, human
  • Guanine Nucleotide Exchange Factors
  • Membrane Proteins
  • Neoplasm Proteins
  • RASGRP2 protein, human