Recessive myosin myopathy with external ophthalmoplegia associated with MYH2 mutations
Recessive myosin myopathy with external ophthalmoplegia associated with MYH2 mutations
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DOI：
10.1038/ejhg.2013.250
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发表时间：
2014-06-01
影响因子：
5.2
通讯作者：
Oldfors, Anders
中科院分区：
文献类型：
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作者：
Tajsharghi, Homa;Hammans, Simon;Oldfors, Anders
肌球蛋白肌病包括一组由肌球蛋白重链（MyHC）基因突变引起的遗传性疾病。纯合子或复合杂合子截断MYH2突变已被证明可引起隐性肌病，包括眼麻痹、轻度至中度肌肉无力和完全缺乏2A型肌纤维。在这项研究中，我们首次描述了与MYH2错义突变相关的隐性肌球蛋白IIa肌病的临床和形态学特征。本文研究了5个不同家族的7例以眼麻痹和轻至中度肌肉无力为特征的肌病患者。肌肉活检研究形态学变化和MyHC亚型表达。5例患者为MYH2错义突变纯合，1例患者为错义突变和无义突变复合杂合，1例患者为MYH2移框突变纯合。肌肉活检显示2A型肌纤维小或缺失，相应的MyHC IIa转录物和蛋白表达减少或缺失。我们得出结论，轻度肌肉无力和眼麻痹结合肌肉活检显示2A型肌纤维小或缺失是隐性肌病与MYH2突变相关的标志。
Myosin myopathies comprise a group of inherited diseases caused by mutations in myosin heavy chain (MyHC) genes. Homozygous or compound heterozygous truncating MYH2 mutations have been demonstrated to cause recessive myopathy with ophthalmoplegia, mild-to-moderate muscle weakness and complete lack of type 2A muscle fibers. In this study, we describe for the first time the clinical and morphological characteristics of recessive myosin IIa myopathy associated with MYH2 missense mutations. Seven patients of five different families with a myopathy characterized by ophthalmoplegia and mild-to-moderate muscle weakness were investigated. Muscle biopsy was performed to study morphological changes and MyHC isoform expression. Five of the patients were homozygous for MYH2 missense mutations, one patient was compound heterozygous for a missense and a nonsense mutation and one patient was homozygous for a frame-shift MYH2 mutation. Muscle biopsy demonstrated small or absent type 2A muscle fibers and reduced or absent expression of the corresponding MyHC IIa transcript and protein. We conclude that mild muscle weakness and ophthalmoplegia in combination with muscle biopsy demonstrating small or absent type 2A muscle fibers are the hallmark of recessive myopathy associated with MYH2 mutations.