Whole-exome sequencing identifies mutations in MYMK in a mild form of Carey-Fineman-Ziter syndrome

Fusion of single-nucleated myoblasts is essential for the formation of multinucleated myocytes. Mechanisms that regulate myoblast fusion have been a focus of recent studies.1–4 Transmembrane protein 8 (TMEM8C), also known as myomaker, is a highly conserved muscle-specific transmembrane protein encoded by the MYMK gene. The protein is expressed during early muscle development. Mymk -null mice die soon after birth because of skeletal muscle deficiency. In these mice, skeletal muscle tissue is present but consists of a smaller number of mononucleated cells indicating failure of myoblast cell fusion.1 Myomaker is also expressed during muscle regeneration when it coordinates fusion of satellite cells with residual muscle fibers to regenerate the damaged muscle tissue. In the absence of myomaker, adult mouse muscle tissue is unable to regenerate.5 The authors are grateful to the patient reported here for giving them permission to share his data and his photographs. They are also grateful to the Newcastle MRC Centre Biobank for Neuromuscular Diseases. Diagnostic facilities at the John Walton Muscular Dystrophy Research Centre are supported by the Nationally Commissioned Highly Specialised Service (HSS) for Neuromuscular Diseases (NHS England). The authors thank Dr. Tuomo Polvikoski from The Newcastle upon Tyne Hospitals NHS Foundation Trust for his help in interpreting muscle biopsy images. They also thank Dr. Chiara Marini Bettolo and Dr. Michela Guglieri from the MRC Centre for Neuromuscular Diseases for their help with clinical logistics.