Abstract: ObjectiveTo clarify the genetic etiology and clinical diagnostic value of familial thrombocytopenia caused by the mutations in the MYH9 gene encoding non-muscle myosin heavy chain IA （NMMHC-IIA) through genetic analysis and pedigree investigation.MethodsThe proband and six family members were performed the complete blood counts, blood smear examination, whole exome sequencing (WES), and Sanger sequencing validation. The pathogenicity of the mutations was analyzed using the bioinformatics tools.ResultsFour family members were identified as heterozygous carriers with the missense mutation c.5521G>A(p.Glul841Lys) in the MYH9gene. They presented with thrombocytopenia（[48-76]x10°/L)，macrothrombocytes，and granulocyte Dohle-like inclusions.Two of them exhibited non-hematological phenotypes such as hearing loss,cataracts，and renal dysfunction. The mutation was located in the coiled-coil domain of the NMMHC-IIA protein. Both Mutation Taster and PolyPhen-2 bioinformatics software analysis indicated that this variant was pathogenic and co-segregated with the phenotype. ConclusionThe pedigre investigation and genetic testing confirm the association of the c.5521G>A mutation in the MYH9 gene with hereditary thrombocytopenia in this family. The combination of blood smear examination with high-throughput sequencing can effectively diagnose MYH9-related diseases （MYH9-RD)， avoiding misdiagnosis as immune thrombocytopenia （ITP).