Leeds Institute of Molecular Medicine, The University of Leeds, UK.
Nat Genet. 2011 Nov 20;43(12):1189-92. doi: 10.1038/ng.995.
Infantile myopathies with diaphragmatic paralysis are genetically heterogeneous, and clinical symptoms do not assist in differentiating between them. We used phased haplotype analysis with subsequent targeted exome sequencing to identify MEGF10 mutations in a previously unidentified type of infantile myopathy with diaphragmatic weakness, areflexia, respiratory distress and dysphagia. MEGF10 is highly expressed in activated satellite cells and regulates their proliferation as well as their differentiation and fusion into multinucleated myofibers, which are greatly reduced in muscle from individuals with early onset myopathy, areflexia, respiratory distress and dysphagia.
婴儿型肌病伴膈肌麻痹具有遗传异质性，临床症状无法帮助区分它们。我们使用分相单体型分析，随后进行靶向外显子组测序，鉴定出一种以前未被识别的婴儿型肌病伴膈肌无力、反射消失、呼吸窘迫和吞咽困难的 MEGF10 突变。MEGF10 在激活的卫星细胞中高表达，调节其增殖以及分化和融合为多核肌纤维，在早发性肌病、反射消失、呼吸窘迫和吞咽困难患者的肌肉中，这些肌纤维大大减少。
