肌球蛋白重链基因在人类遗传性疾病中的研究进展.pdfVIP

肌球蛋白重链基因在人类遗传性疾病中的研究进展 何一旻，顾鸣敏 上海交通大学医学院医学遗传学实验室，上海 200025 摘要：肌球蛋白超家族通过水解ATP ，将化学能转化为机械能，在细胞迁移、肌肉收缩等多种生理活动中发挥重要的作用。其中， 肌球蛋白II 类分子是肌细胞和非肌细胞中肌丝的重要组成成分。一个完整的肌球蛋白II 类分子是由2 条肌球蛋白重链(myosin heavy chain ，MyHC)和2 对不同的轻链组成的六聚体。在人体中，存在多种MyHC 亚型，分别由不同的MYH 基因家族成员编码。迄今 为止，人们已经发现MYH 基因家族中多个成员的不同突变与人类遗传性疾病相关。其中，MYH2 突变可以导致一类以眼肌麻痹为 主要特征的骨骼肌疾病；MYH3 和MYH8 突变可以引起远端关节挛缩综合征；MYH7 突变即可以引起骨骼肌疾病包括肌球蛋白沉 积性肌病和Laing 远端肌病，也与肥厚性心肌病的发生密切相关；MYH9 突变可以导致一类以巨大血小板、血小板减少和中性粒细 胞包涵体为特征的MYH9-相关性疾病。本文简要介绍MYH 基因的表达特点，着重阐述MYH 基因与人类遗传性疾病之间的相关性 及研究进展。 关键词：MYH 基因家族；肌球蛋白重链；遗传性疾病 Research progress of myosin heavy chain genes in human genetic diseases Yimin He, Mingmin Gu Medical Genetics Lab , Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China Abstract: Myosins constitute a large superfamily proteins, which convert chemical energy, through ATP hydrolysis, to mechanical force for diverse cellular movements, such as cell migration and muscle contraction. The class II myosin forms the filaments in muscle and non-muscle cells as a hexameric protein complex, consisting of two myosin heavy chain (MyHC) subunits and two pairs of non-identical light chain subunits. There are several MyHC isoforms encoded by different genes of the MYH family in humans. At present, distinct mutations in different genes of the MYH family are associated with various human genetic diseases. Mutations in MYH2 are associated with skeletal myopathies, characterized by ophthalmoplegia. Mutations in MYH3 and MYH8 are associated with distal arthrogryposis syndromes. Mutations in MYH7 are associated with not only skeletal muscle diseases, such as Laing distal myopathy and myosin storage myopathy, but also hypertrophic cardiomyopathy. Mutations in MYH9 are associated with the so-called MYH9-related disease, characterized by giant platelets, thrombocytopenia and granulocyte inclusions. In this review, we briefl