Genetic analysis of a pedigree affected with inherited thrombocytopenia caused by a novel mutation of MYH9 gene / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To study genetic mutations and clinical features of a pedigree affected with MYH9-related disorders from Guangxi.</p><p><b>METHODS</b>Blood platelets were counted with a hemocytometer. Blood smear was carried out to detect the inclusion body in peripheral blood neutrophils. DNA and mRNA samples were extracted from blood samples from the members of the pedigree. Fragments of the MYH9 gene were amplified with PCR and directly sequenced.</p><p><b>RESULTS</b>The affected individuals presented with a triad of giant platelets, decreased platelet count and inclusion bodies in the neutrophils with variable expressivity. A heterozygous deletional mutation (c.5803delG) in exon 41 of the MYH9 gene was found in all of the 8 affected individuals, which led to a frame-shift and change of 26 amino acids at the C-end of the tail domain of nonmuscle myosin heavy chain IIA (NMMHC-IIA) (p.Ala1935Profs*12). The same mutation was not found among healthy members of the pedigree.</p><p><b>CONCLUSION</b>The c.5803delG mutation probably underlies the MYH9-related disorders in this pedigree. The mutation has altered the C-end of the tail domain of the NMMHC-IIA protein, resulting in mild clinical symptoms in the affected individuals.</p>