Molecular pathogenesis of MYH9 disorders

MYH 9疾病是常染色体显性遗传的先天性血小板疾病，其特征在于巨大血小板、血小板减少症和粒细胞包涵体。转染野生型全长MYH 9 cDNA的COS 7细胞和在患者中鉴定的外显子40的单碱基缺失突变的COS 7细胞显示NMMHC-IIA蛋白的正常纤维定位，不形成包涵体。在转染的COS 7细胞中，无论是否有MYH 9突变，板状脂质体延伸的抑制和粘着斑复合物数量的增加表明突变型NMMHC-IIA的功能性表达。

The MYH9 disorders are autosomal dominant congenital platelet disorders, characterized by giant platelets, thrombocytopenia, and granulocyte inclusion bodies. COS7 cells transfected with wild-type full length MYH9 cDNA and that with the single base deletion mutation of Exon 40 identified in patients showed the normal fiber localization of NMMHC-IIA protein without forming inclusion bodies. Inhibition of lamellipodial extension and increase in the number of focal adhesion complex in transfected COS7 cells, with or without MYH9 mutation, suggested functional expression of mutant NMMHC-IIA.