Thrombocytopenia Caused By Compound Heterozygous Missense Mutations C.3946G>a in Vwf Gene and C.1825C>T in MYO5A Gene?

Objective: One patient with thrombocytopenia from childhood was examined to identify the cause of thrombocytopenia.

Methods: The previous medical history of the patient was comprehensively reviewed, with blood routine examination , reticular platelet count, autoantibodies, hepatitis virus full set, thyroid function, plasma coagulation factor VIII activity, vWF activity and antigen testing, and NGS with peripheral blood to detect thrombosis and hemostatic related genes.

Results: The female patient, 43 years old, was presented with thrombocytopenia for more than 40 years. She had no history of fever or bleeding with no significant menstrual volume increasing. His father had similar thrombocytopenia but died four years ago. On third June,2021, she had no skin bruises or enlarged spleen. Blood routine test showed wbc 7.4x10 ⁹/l, HB 112g/l, Plt 47x10 ⁹/l and reticular platelet count 1.85%. Hepatitis B surface antibody was 147.08mIU/ml. FVIII:C was 62.0% with vWF:A 17.4% and vWF:Ag 61.9%. NGS results suggested that there was a heterozygous c.3946G> A missense mutations in Exon28 of vWF gene (chr12:6128638) , resulting in p.Val1316Met. The variation is rare in the East Asian population and is shown in the human disease database to cause type 2B vWD, which causes increased platelet clearance due to variation in vWF molecule-platelet binding regions, clinically manifested as mild to moderate platelet reduction. there was also a heterozygous c.1825C>T missense mutation in Exon15 of MYO5A gene (chr15:52676447) , resulting in p.Arg609Cys. There are adverse effects on the structure / function of the MYH12 protein encoded by the MYO5A gene. The MYH12 protein is involved in cell metabolism and cytoskeletal activity, and this protein deficiency might also cause thrombocytopenia, which is clearly warranted to further investigation.

Conclusions：compound heterozygous missense mutations c.3946G>A in vWF gene and c.1825C>T in MYO5A gene might caused thrombocytopenia in the patient.