Molecular pathogenesis of MYH9 disorders

Myh9疾病是常染色体显性遗传的先天性血小板疾病，其特征是巨大的血小板、血小板减少和粒细胞包涵体。转染野生型全长Myh9基因的COS7细胞和患者外显子40单碱基缺失突变的COS7细胞显示NMMHC-IIA蛋白的纤维定位正常，没有形成包涵体。无论有没有Myh9突变，COS7细胞的片脂伸展受到抑制，粘着斑数增加，提示突变的NMMHC-IIA具有功能表达。

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.