Deleterious mutation in the FYB gene is associated with congenital autosomal recessive small‐platelet thrombocytopenia

摘要: SummaryBackground The FYB gene encodes adhesion and degranulation-promoting adaptor protein (ADAP), a hematopoietic-specific involved in platelet activation, cell motility proliferation, integrin-mediated adhesion. No ADAP-related diseases have been described humans, but ADAP-deficient mice mild thrombocytopenia increased rebleeding from tail wounds. Patients methods We studied previously reported family of five children two consanguineous sibships Arab Christian descent affected with novel autosomal recessive bleeding disorder small-platelet thrombocytopenia. Homozygosity mapping exome sequencing were used to identify the genetic lesion causing disease phenotype on chromosome 5. Bone-marrow morphology function analyzed. Platelets characterized by scanning electron microscopy. Results We identified homozygous deleterious nonsense mutation, c.393G>A, FYB. A reduced percentage mature megakaryocytes was found bone marrow. Patients’ platelets showed basal expression P-selectin PAC-1, increments activation markers after stimulation ADP, as detected flow cytometry; they also pseudopodium formation presence trapped between fibrin fibers thrombin addition, observed microscopy. Conclusions This is first report caused an defect manifested remarkable significant tendency. The shows ADAP be important for normal production, morphologic changes, function. It suggested that mutation analysis this included diagnosis inherited