Kerst et al. (2000) reported a boy with a mild form of centronuclear myopathy. He showed the first signs of myopathy at the age of 9 years when creatine kinase serum activities were elevated to 300-560 U/l. Three ... Kerst et al. (2000) reported a boy with a mild form of centronuclear myopathy. He showed the first signs of myopathy at the age of 9 years when creatine kinase serum activities were elevated to 300-560 U/l. Three years later, creatine kinase activities were normal, but he complained of muscle cramps and weakness in his lower limbs during vigorous exercise. At that time, histologic muscle analysis showed myopathic changes with ring fibers and an increased percentage of central nuclei fibers.
In a boy with myopathy and an increase of muscle fibers with centralized nuclei, Kerst et al. (2000) detected a heterozygous mutation in the MYF6 gene (A112S; 159991.0001). Protein-protein interaction of mutant MYF6 was reduced, and DNA-binding potential ... In a boy with myopathy and an increase of muscle fibers with centralized nuclei, Kerst et al. (2000) detected a heterozygous mutation in the MYF6 gene (A112S; 159991.0001). Protein-protein interaction of mutant MYF6 was reduced, and DNA-binding potential and transactivation capacity were abolished, thus demonstrating MYF6 haploinsufficiency. The boy's father, who had a pathogenic deletion in the dystrophin gene (DMD; 300377) associated with Becker muscular dystrophy (300376), also carried the MYF6 mutation. The father had a severe disease course, suggesting MYF6 as a modifier of the phenotype. The father presented with cardiomyopathy, pectus carinatum, and severe muscular dystrophy, and was wheelchair-bound by the age of 21 years. Muscle biopsy studies revealed massive fibrosis and discontinuous patchy immunostaining of dystrophin. This was said to be the first observation of a pathogenic defect of an MYF mutation in man.