Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Backer muscular dystrophy

Myogenic factors (MYF) belong to the basic helix-loop-helix (bHLH) transcri ption factor family and regulate myogenesis and muscle regeneration. The ph ysiological importance of both functions was demonstrated in homozygous Myf knockout mice and mdx mice. Myf5 and Myod are predominantly expressed in p roliferating myoblasts while Myf4 and Myf6 are involved in differentiation of myotubes. In a boy with myopathy and an increase of muscle fibres with c entral nuclei we detected a heterozygous 387G --> T nucleotide transversion in the MYF6 gene (MIM*159991). Protein-protein interaction of mutant MYF6 was reduced, and DNA-binding potential and transactivation capacity were ab olished. thus demonstrating MYF6 haploinsufficiency. The boy's father carri ed the identical mutation and, in addition, an in-frame deletion of exons 4 5-47 in his dystrophin gent. This mutation is normally associated with a mi ld to moderate course of Becker muscular dystrophy but the father suffered from a severe course of Becker muscular dystrophy suggesting MYF6 as a modi fier. (C) 2000 Elsevier Science B.V. All rights reserved.