A de novo mutation of the MYH7 gene in a large Chinese family with autosomal dominant myopathy.
A de novo mutation of the MYH7 gene in a large Chinese family with autosomal dominant myopathy.
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一个患有常染色体显性肌病的中国大家族中 MYH7 基因的从头突变
DOI：
10.1038/hgv.2015.22
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发表时间：
2015
影响因子：
1.5
通讯作者：
Toda T
中科院分区：
文献类型：
--
作者：
Oda T;Xiong H;Kobayashi K;Wang S;Satake W;Jiao H;Yang Y;Cha PC;Hayashi YK;Nishino I;Suzuki Y;Sugano S;Wu X;Toda T
莱氏远端肌病是一种常染色体显性遗传性肌病，由慢/β心肌肌球蛋白重链(MYH7)基因突变引起。最近有报道称LDM具有广泛的临床表现。我们在此报告一个常染色体显性遗传性肌病的中国大家族。家庭中受影响的个体在童年早期表现为足下垂，并伴有进行性远端和近端肢体无力。其特征性症状包括早期的肩胛翼和脊柱侧弯，以及晚期的行走障碍。虽然最初怀疑为肢带型肌营养不良症(LGMD)，但无法得出明确的诊断。因此，我们进行了连锁分析，检测到四个连锁区域，即1q23.2-24.1、14q11.2-12、15q26.2-26.3和17q24.3。通过随后的整个外显子组测序，我们在MYH7基因上发现了一个新的P.K1617del致病突变，并诊断为LDM。这是中国就诊的首例腰椎间盘突出症。与其他地方报道的具有相同突变的患者相比，我们的患者具有严重的临床表现，类似于LGMD。
Laing distal myopathy (LDM) is an autosomal dominant myopathy that is caused by mutations in the slow/beta cardiac myosin heavy-chain (MYH7) gene. It has been recently reported that LDM presents with a wide range of clinical manifestations. We herein report a large Chinese family with autosomal dominant myopathy. The affected individuals in the family presented with foot drop in early childhood, along with progressive distal and proximal limb weakness. Their characteristic symptoms include scapular winging and scoliosis in the early disease phase and impairment of ambulation in the advanced phase. Although limb-girdle muscle dystrophy (LGMD) was suspected initially, a definite diagnosis could not be reached. As such, we performed linkage analysis and detected four linkage regions, namely 1q23.2-24.1, 14q11.2-12, 15q26.2-26.3 and 17q24.3. Through subsequent whole exome sequencing, we found a de novo p.K1617del causative mutation in the MYH7 gene and diagnosed the disease as LDM. This is the first LDM case in China. Our patients have severe clinical manifestations that mimic LGMD in comparison with the patients with the same mutation reported elsewhere.