G.P.153: Recessive myosin myopathy with external ophthalmoplegia associated with MYH2 mutations

Abstract

Myosin myopathies comprise a group of inherited diseases caused by mutations in myosin heavy chain (MyHC) genes. Homozygous or compound heterozygous truncating MYH2 mutations have been demonstrated to cause recessive myopathy with ophthalmoplegia, mild to moderate muscle weakness and complete lack of type 2A muscle fibers. In this study, we describe the clinical and morphological characteristics of recessive MYH2 missense mutations. Seven patients of five different families with a myopathy characterized by ophthalmoplegia and mild to moderate muscle weakness were investigated. Muscle biopsy was performed to study morphological changes and MyHC isoform expression. Five of the patients were homozygous for MYH2 missense mutations, one patient was compound heterozygous for a missense and a nonsense mutation and one patient was homozygous for a frame-shift MYH2 mutation. Muscle biopsy demonstrated morphologically abnormal or absent type 2A muscle fibers and reduced or absent expression of the corresponding MyHC IIa transcript and protein. We conclude that missense mutations in MYH2 may cause a recessively inherited myopathy associated with external ophthalmoplegia, similar to that of truncating MYH2 mutations, but with different type 2 fiber pathology.