title: 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 for the first time the clinical and morphological characteristics of recessive myosin IIa myopathy associated with 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 small or absent type 2A muscle fibers and reduced or absent expression of the corresponding MyHC IIa transcript and protein. We conclude that mild muscle weakness and ophthalmoplegia in combination with muscle biopsy demonstrating small or absent type 2A muscle fibers are the hallmark of recessive myopathy associated with MYH2 mutations.
authors.affiliation: Department of Pathology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Homa
authors.initials: H
authors.lastname: Tajsharghi
authors.affiliation: Wessex Neurological Centre, Southampton General Hospital, Southampton, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Hammans
authors.affiliation: Department of Neurology, Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Hospital, Gothenburg, Sweden.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lindberg
authors.affiliation: Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lossos
authors.affiliation: Institute for Neuromuscular Research, Children's Hospital at Westmead and Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Nigel F
authors.initials: NF
authors.lastname: Clarke
authors.affiliation: Cellular Pathology, Southampton General Hospital, Southampton, UK.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Mazanti
authors.affiliation: Institute for Neuromuscular Research, Children's Hospital at Westmead and Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Leigh B
authors.initials: LB
authors.lastname: Waddell
authors.affiliation: Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Yakov
authors.initials: Y
authors.lastname: Fellig
authors.affiliation: Wessex Clinical Genetics Services, UHS NHS Foundation Trust, Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Foulds
authors.affiliation: Wessex Neurological Centre, Southampton General Hospital, Southampton, UK.
authors.forename: Haider
authors.initials: H
authors.lastname: Katifi
authors.affiliation: Department of Neurology, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Webster
authors.affiliation: Neuromuscular Research Unit, Tampere University and Hospital, Tampere, Finland.
authors.forename: Olayinka
authors.initials: O
authors.lastname: Raheem
authors.affiliation: 1] Neuromuscular Research Unit, Tampere University and Hospital, Tampere, Finland [2] Department of Neurology, Vasa Central Hospital, Vasa, Finland [3] Department of Medical Genetics, Folkhälsan Genetic Institute, Helsinki University, Helsinki, Finland.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Udd
authors.affiliation: Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Argov
authors.affiliation: Department of Pathology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Oldfors
mesh_terms: D000328:Adult; D001706:Biopsy; D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D015870:Gene Expression; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018656:Muscle Fibers, Fast-Twitch / Q000473:pathology; D018908:Muscle Weakness / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense; D018995:Myosin Heavy Chains / Q000235:genetics*; D009886:Ophthalmoplegia / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018389:Codon, Nonsense; D018995:Myosin Heavy Chains