title: A novel MYH7 mutation links congenital fiber type disproportion and myosin storage myopathy.
abstract: This study aimed to identify the genetic defect in a multigenerational family presenting an autosomal dominant myopathy with histological features of congenital fiber type disproportion. Linkage analysis and genetic sequencing identified, in all affected members of the family, the c.5807A>G heterozygous mutation in MYH7, which encodes the slow/β-cardiac myosin heavy chain. This mutation causes skeletal but not cardiac involvement. Myosin heavy chain expression pattern was also characterized by immunohistochemistry, western blot and q-PCR in muscle biopsies from two patients aged 25 and 62, respectively. While only congenital fiber type disproportion was observed in the younger patient, older patient's biopsy presented aggregates of slow myosin heavy chains, in fiber sub-sarcolemmal region. These clinico-pathologic findings suggest a novel phenotype within the emerging group of hereditary myosin myopathies, which in this family presents typical characteristics of congenital fiber type disproportion in early stages and later evolves to myosin storage myopathy.
authors.affiliation: Department of Pathology and Neuropathology, University Hospital of Vigo (Meixoeiro), Vigo, Spain.
authors.forename: Saida
authors.initials: S
authors.lastname: Ortolano
authors.forename: Rosa
authors.initials: R
authors.lastname: Tarrío
authors.forename: Patricia
authors.initials: P
authors.lastname: Blanco-Arias
authors.forename: Susana
authors.initials: S
authors.lastname: Teijeira
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodríguez-Trelles
authors.forename: María
authors.initials: M
authors.lastname: García-Murias
authors.forename: Valerie
authors.initials: V
authors.lastname: Delague
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lévy
authors.forename: José M
authors.initials: JM
authors.lastname: Fernández
authors.forename: Beatriz
authors.initials: B
authors.lastname: Quintáns
authors.forename: Beatriz San
authors.initials: BS
authors.lastname: Millán
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: María-Jesús
authors.initials: MJ
authors.lastname: Sobrido
mesh_terms: D001483:Base Sequence; D024722:Cardiac Myosins / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005190:Family; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology; D008040:Genetic Linkage; D006801:Humans; D007150:Immunohistochemistry; D007536:Isomerism; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology*; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000235:genetics*; D009218:Myosins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012313:RNA / Q000096:biosynthesis / Q000235:genetics
chemical_list: C501641:MYH7 protein, human; D012313:RNA; D004247:DNA; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains; D009218:Myosins