Recessive thrombocytopenia likely due to a homozygous pathogenic variant in the FYB gene: case report

BMC Med Genet. 2014 Dec 17:15:135. doi: 10.1186/s12881-014-0135-0.


Background: Inherited thrombocytopenias (IT) are a heterogeneous group of rare diseases characterized by a reduced number of blood platelets. The frequency of IT is probably underestimated because of diagnostic difficulties and because not all the existing forms have as yet been identified, with some patients remaining without a definitive diagnosis. Exome Sequencing has made possible the identification of almost all variants in the coding regions of protein-coding genes, thereby providing the opportunity to identify the disease causing gene in a number of patients with indefinite diagnoses, specifically in consanguineous families.

Case presentation: Familial thrombocytopenia with small size platelets was present in several members of a highly consanguineous family from Northern Iraq. Genotyping of all affected, their unaffected siblings and parents, followed by exome sequencing revealed a strong candidate loss of function variant in a homozygous state: a frameshift mutation in the FYB gene. The protein encoded by this gene is known to be a cytosolic adaptor molecule expressed by T, natural killer (NK), myeloid cells and platelets, and is involved in platelet activation and controls the expression of interleukin-2. Knock-out mice were reported to show isolated thrombocytopenia.

Conclusion: Inherited thrombocytopenias differ in their presentation, associated features, and molecular etiologies. An accurate diagnosis is needed to provide appropriate management as well as counseling for the individuals and their family members. Exome sequencing may become a first diagnostic tool to identify the molecular basis of undiagnosed familial IT. In this report, the clinical evaluation combined with the power and efficiency of genomic analysis defined the FYB gene as the possible underlying cause of autosomal recessive thrombocytopenia with small platelet size. This is the first report linking pathogenic variants in FYB and thrombocytopenia in humans.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • DNA Mutational Analysis
  • Exome
  • Female
  • Frameshift Mutation
  • Genes, Recessive
  • Humans
  • Infant
  • Iraq
  • Male
  • Pedigree
  • Thrombocytopenia / genetics*


  • Adaptor Proteins, Signal Transducing
  • FYB1 protein, human