A de novo mutation of the MYH7 gene in a large Chinese family with autosomal dominant myopathy

Tetsuya Oda; Hui Xiong; Kazuhiro Kobayashi; Shuo Wang; Wataru Satake; Hui Jiao; Yanling Yang; Pei-Chieng Cha; Yukiko K Hayashi; Ichizo Nishino; Yutaka Suzuki; Sumio Sugano; Xiru Wu; Tatsushi Toda

doi:10.1038/hgv.2015.22

A de novo mutation of the MYH7 gene in a large Chinese family with autosomal dominant myopathy

Hum Genome Var. 2015 Jul 16:2:15022. doi: 10.1038/hgv.2015.22. eCollection 2015.

Authors

Affiliations

¹ Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine , Kobe, Japan.
² Department of Pediatrics, Peking University First Hospital , Beijing, China.
³ Department of Pathophysiology, Tokyo Medical University , Tokyo, Japan.
⁴ Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry , Tokyo, Japan.
⁵ Department of Computational Biology, Graduate School of Frontier Sciences, the University of Tokyo , Chiba, Japan.
⁶ Laboratory of Functional Genomics, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, the University of Tokyo , Tokyo, Japan.

Abstract

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.