A novel MYH2 mutation in family members presenting with congenital myopathy, ophthalmoplegia and facial weakness
A novel MYH2 mutation in family members presenting with congenital myopathy, ophthalmoplegia and facial weakness
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DOI：
10.1007/s00415-016-8154-8
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发表时间：
2016-07-01
影响因子：
6
通讯作者：
Oldfors, Anders
中科院分区：
文献类型：
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作者：
Willis, Tracey;Hedberg-Oldfors, Carola;Oldfors, Anders
肌球蛋白重链（MyHC）是横纹肌收缩器的主要结构成分。在成年人肢体骨骼肌中，存在三种主要的MyHC同种型，慢/β心脏MyHC、MyHC IIa和MHC IIx，它们对于不同肌纤维类型的功能特征是重要的。遗传性肌球蛋白肌病已经成为一组重要的疾病，其临床和形态学表达依赖于突变的同种型，以及突变的类型和位置。伴有眼外肌麻痹的肌球蛋白肌病与MYH 2突变相关，MYH 2编码MyHC IIa，主要在2A型肌纤维中表达，并以显性和隐性方式遗传。我们提出一个家族肌病与早发近端肌无力，面部肌肉参与和眼肌麻痹。肌肉活检证实缺乏2A型肌纤维，遗传学检查证实该疾病是由一种新型隐性MYH 2突变引起的：c.1009-1G > A，导致外显子12跳读，预计这将导致移码并在位置347处引入提前终止密码子（p.Ser337Leufs*11）。
Myosin heavy chain (MyHC) is a major structural component of the striated muscle contractile apparatus. In adult human limb skeletal muscle, there are three major MyHC isoforms, slow/beta cardiac MyHC, MyHC IIa and MHC IIx, which are important for the functional characteristics of different muscle fiber types. Hereditary myosin myopathies have emerged as an important group of diseases with variable clinical and morphological expression dependent on the mutated isoform, and also the type and location of the mutation. Myosin myopathy with external ophthalmoplegia is associated with mutations in MYH2, encoding for MyHC IIa that is mainly expressed in type 2A muscle fibers and is inherited in dominant as well as recessive manner. We present a family with myopathy with early onset proximal muscle weakness, facial muscle involvement and ophthalmoplegia. Muscle biopsy demonstrated lack of type 2A muscle fibers and genetic work up demonstrated that the disease was caused by a novel recessive MYH2 mutation: c.1009-1G > A resulting in skipping of exon 12, which is predicted to result in a frame shift and introducing at premature stop codon at position 347 (p.Ser337Leufs*11).