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 &...

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Published in:Neuromuscular disorders : NMD 2011-04, Vol.21 (4), p.254-262
Main Authors: Ortolano, Saida, Tarrío, Rosa, Blanco-Arias, Patricia, Teijeira, Susana, Rodríguez-Trelles, Francisco, García-Murias, María, Delague, Valerie, Lévy, Nicolas, Fernández, José M, Quintáns, Beatriz, Millán, Beatriz San, Carracedo, Ángel, Navarro, Carmen, Sobrido, María-Jesús
Format: Article
Language:English
Subjects:
Base Sequence
Cardiac Myosins - genetics
Congenital fiber type disproportion
DNA - chemistry
DNA - genetics
Family
Fluorescent Antibody Technique
Gene Expression Regulation - physiology
Genetic Linkage
Humans
Immunohistochemistry
Isomerism
Microscopy, Electron
Molecular Sequence Data
Muscle Fibers, Skeletal - pathology
Muscle, Skeletal - pathology
Muscular Diseases - genetics
Muscular Diseases - pathology
Mutation
Mutation - genetics
Mutation - physiology
MYH7
Myosin Heavy Chains - genetics
Myosin storage myopathy
Myosins - chemistry
Myosins - genetics
Neurology
Pedigree
Phenotype
RNA - biosynthesis
RNA - genetics
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Summary: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.
ISSN:0960-8966
1873-2364
DOI:10.1016/j.nmd.2010.12.011