Identification of a Novel MPL Loss of Function Mutation in a Patient with Cyclic Thrombocytopenia and Characterization of This Syndrome

The study identified a novel MPL loss-of-function mutation in a 53-year-old male patient with cyclic thrombocytopenia (CT), characterized by periodic fluctuations in platelet counts. The patient's platelet counts ranged from 1 x 10^9/L to over 400 x 10^9/L in a 40-day cycle. The research involved blood transcriptome profiling and plasma cytokine analysis, revealing significant gene expression changes in neutrophil- and platelet-specific genes preceding platelet count fluctuations. A novel MPL c.1210G>A heterozygous mutation, causing a p.Gly404Arg substitution, was found in the patient's blood and hair follicle DNA. This mutation was predicted to be deleterious, creating a novel splice site and resulting in a loss-of-function variant. The study concluded that cyclic megakaryopoiesis and thrombopoiesis underlie the disease's pathogenesis, with the identified MPL mutation potentially contributing to the condition.