title: A novel MYH2 mutation in family members presenting with congenital myopathy, ophthalmoplegia and facial weakness.
abstract: Myosin heavy chain (MyHC) is a major structural component of the striated muscle contractile apparatus. In adult human limb skeletal muscle, there are three major MyHC isoforms, slow/beta cardiac MyHC, MyHC IIa and MHC IIx, which are important for the functional characteristics of different muscle fiber types. Hereditary myosin myopathies have emerged as an important group of diseases with variable clinical and morphological expression dependent on the mutated isoform, and also the type and location of the mutation. Myosin myopathy with external ophthalmoplegia is associated with mutations in MYH2, encoding for MyHC IIa that is mainly expressed in type 2A muscle fibers and is inherited in dominant as well as recessive manner. We present a family with myopathy with early onset proximal muscle weakness, facial muscle involvement and ophthalmoplegia. Muscle biopsy demonstrated lack of type 2A muscle fibers and genetic work up demonstrated that the disease was caused by a novel recessive MYH2 mutation: c.1009-1G>A resulting in skipping of exon 12, which is predicted to result in a frame shift and introducing at premature stop codon at position 347 (p.Ser337Leufs*11).
authors.affiliation: Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, SY10 7AG, UK.
authors.forename: Tracey
authors.initials: T
authors.lastname: Willis
authors.affiliation: Department of Pathology and Genetics, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden.
authors.forename: Carola
authors.initials: C
authors.lastname: Hedberg-Oldfors
authors.affiliation: Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, SY10 7AG, UK.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Alhaswani
authors.affiliation: Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, SY10 7AG, UK.
authors.forename: Richa
authors.initials: R
authors.lastname: Kulshrestha
authors.affiliation: Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, SY10 7AG, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sewry
authors.affiliation: Department of Pathology and Genetics, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden. anders.oldfors@gu.se.
authors.forename: Anders
authors.initials: A
authors.lastname: Oldfors
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005152:Facial Muscles / Q000503:physiopathology; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018908:Muscle Weakness / Q000150:complications / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D009224:Myotonia Congenita / Q000150:complications / Q000235:genetics*; D009886:Ophthalmoplegia / Q000150:complications / Q000235:genetics*
chemical_list: D018995:Myosin Heavy Chains
keywords: MYH2; Myopathy; Myosin; Ophthalmoplegia