title: Novel mutations widen the phenotypic spectrum of slow skeletal/β-cardiac myosin (MYH7) distal myopathy.
abstract: Laing early onset distal myopathy and myosin storage myopathy are caused by mutations of slow skeletal/β-cardiac myosin heavy chain encoded by the gene MYH7, as is a common form of familial hypertrophic/dilated cardiomyopathy. The mechanisms by which different phenotypes are produced by mutations in MYH7, even in the same region of the gene, are not known. To explore the clinical spectrum and pathobiology, we screened the MYH7 gene in 88 patients from 21 previously unpublished families presenting with distal or generalized skeletal muscle weakness, with or without cardiac involvement. Twelve novel mutations have been identified in thirteen families. In one of these families, the father of the proband was found to be a mosaic for the MYH7 mutation. In eight cases, de novo mutation appeared to have occurred, which was proven in four. The presenting complaint was footdrop, sometimes leading to delayed walking or tripping, in members of 17 families (81%), with other presentations including cardiomyopathy in infancy, generalized floppiness, and scoliosis. Cardiac involvement as well as skeletal muscle weakness was identified in nine of 21 families. Spinal involvement such as scoliosis or rigidity was identified in 12 (57%). This report widens the clinical and pathological phenotypes, and the genetics of MYH7 mutations leading to skeletal muscle diseases.
authors.affiliation: Neurogenetic Unit, Department of Neurology, Royal Perth Hospital, Western Australia, Australia; Diagnostic Genomics Laboratory, Pathwest, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia.
authors.forename: Phillipa J
authors.initials: PJ
authors.lastname: Lamont
authors.forename: William
authors.initials: W
authors.lastname: Wallefeld
authors.forename: David
authors.initials: D
authors.lastname: Hilton-Jones
authors.forename: Bjarne
authors.initials: B
authors.lastname: Udd
authors.forename: Zohar
authors.initials: Z
authors.lastname: Argov
authors.forename: Alexandru C
authors.initials: AC
authors.lastname: Barboi
authors.forename: Carsten
authors.initials: C
authors.lastname: Bonneman
authors.forename: Kym M
authors.initials: KM
authors.lastname: Boycott
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: Anne M
authors.initials: AM
authors.lastname: Connolly
authors.forename: Nicholas
authors.initials: N
authors.lastname: Davies
authors.forename: Alan H
authors.initials: AH
authors.lastname: Beggs
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Cox
authors.forename: Jahannaz
authors.initials: J
authors.lastname: Dastgir
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: DeChene
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gooding
authors.forename: Heinz
authors.initials: H
authors.lastname: Jungbluth
authors.forename: Nuria
authors.initials: N
authors.lastname: Muelas
authors.forename: Johanna
authors.initials: J
authors.lastname: Palmio
authors.forename: Sini
authors.initials: S
authors.lastname: Penttilä
authors.forename: Eric
authors.initials: E
authors.lastname: Schmedding
authors.forename: Tiina
authors.initials: T
authors.lastname: Suominen
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.forename: Christopher
authors.initials: C
authors.lastname: Staples
authors.forename: Peter Y K
authors.initials: PY
authors.lastname: Van den Bergh
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Vilchez
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Wagner
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Wheeler
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wraige
authors.forename: Nigel G
authors.initials: NG
authors.lastname: Laing
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D024722:Cardiac Myosins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D049310:Distal Myopathies / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D055815:Young Adult
chemical_list: C501641:MYH7 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains
keywords: Laing distal myopathy; MPD1; MYH7