Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD)

• Published in: Nature genetics Vol. 43; no. 12; pp. 1189 - 1192
• Main Authors: Logan, Clare V, Lucke, Barbara, Pottinger, Caroline, Abdelhamed, Zakia A, Parry, David A, Szymanska, Katarzyna, Diggle, Christine P, van Riesen, Anne, Morgan, Joanne E, Markham, Grace, Ellis, Ian, Manzur, Adnan Y, Markham, Alexander F, Shires, Mike, Helliwell, Tim, Scoto, Mariacristina, Hübner, Christoph, Bonthron, David T, Taylor, Graham R, Sheridan, Eamonn, Muntoni, Francesco, Carr, Ian M, Schuelke, Markus, Johnson, Colin A
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2011; Nature Publishing Group
• Subjects: 631/208/2489/144; Abnormalities, Multiple - genetics; Adolescent; Agriculture; Animal Genetics and Genomics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; brief-communication; Cancer Research; Child; Child, Preschool; Consanguinity; Deglutition disorders; Deglutition Disorders - genetics; Deltoid Muscle - pathology; Esophagus; Female; Frameshift Mutation; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Function; Gene mutations; Genetic aspects; Genetic Association Studies; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Health aspects; Heredity; Human Genetics; Humans; INDEL Mutation; Infant; Infant, Newborn; Male; Medical sciences; Membrane Proteins - genetics; Muscle Development - genetics; Muscle diseases; Muscular Diseases - genetics; Mutation; Mutation, Missense; Other diseases. Semiology; Pedigree; Pneumology; Proteins; Respiratory distress syndrome; Respiratory Distress Syndrome, Newborn - genetics; Respiratory system : syndromes and miscellaneous diseases; Risk factors; Satellite Cells, Skeletal Muscle - metabolism; Sequence Analysis, DNA; Studies; United Kingdom; Respiratory disease; Esophageal disease; ENT disease; Digestive diseases; Respiratory distress; Early; Dysphagia; Mutation; Satellite cell; Myogenesis; Myopathy
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.995

Markus Schuelke, Colin Johnson and colleagues report the identification of mutations in MEGF10 that cause infantile myopathy with diaphragmatic weakness, areflexia, respiratory distress and dysphagia. 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.