Identification of a novel SBF2 missense mutation associated with a rare case of thrombocytopenia using whole-exome sequencing

J Thromb Thrombolysis. 2013 Nov;36(4):501-6. doi: 10.1007/s11239-012-0864-x.


We describe in this report a case of a 6-years-old female who presented at the age of 1 month with a mucocutaneous bleeding and suspected thrombocytopenia. The patient's condition was refractory to the known idiopathic thrombocytopenic purpura treatments and congenital form of Thrombocytopenia was suspected following the delivery of a male sibling with the same phenotype. The patient also manifested fair colored hair and skin relative to her family however she did not have any detectable neurologic or other immunologic abnormalities. In order to further understand this condition, we have used whole-exome sequencing of the patient's DNA as well as her father's with the assumption that her condition is transmitted in an autosomal recessive manner. We have identified a missense change c.659C>G (p.Thr220Arg) in the SBF2 (also known as MTMR13) gene that causes a mutation in the DENN domain of the protein. This mutation was validated by traditional Sanger sequencing and analyzed in the remaining family members were it was found to segregate in the homozygous state in the affected siblings and in the heterozygous state in both parents. This novel mutation in the DENN domain of SBF2 maybe interfering with its putative association with the Rab family of small GTPases which are important mediators of vesicle transport and membrane trafficking. In conclusion, we have identified a novel mutation that is associated with severe thrombocytopenia. The fact that this mutation is found in SBF2 gene may indicate that the underlying cause of thrombocytopenia in our patient is either a new variant form of Griscelli syndrome (through the Rab GTPases action) or a variant Charcot-Marie-Tooth type 4 disease as SBF2 truncating mutations were previously identified in sufferers of this disease. This finding will help to accurately diagnose and classify similar cases of congenital thrombocytopenia and provide further proof to the power of whole-exome sequencing in personalizing patients management from the point of diagnosis to treatment and followup.

Publication types

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

MeSH terms

  • Amino Acid Substitution
  • Child
  • DNA Mutational Analysis
  • Exome*
  • Female
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / metabolism
  • Genetic Diseases, Inborn / pathology
  • Humans
  • Mutation, Missense*
  • Protein Tyrosine Phosphatases, Non-Receptor / genetics*
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism
  • Thrombocytopenia / genetics*
  • Thrombocytopenia / metabolism
  • Thrombocytopenia / pathology


  • Protein Tyrosine Phosphatases, Non-Receptor
  • SBF2 protein, human