MYH7 mutation associated with two phenotypes of myopathy
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The mutations of MYH7 (slow skeletal/β-cardiac myosin heavy chain) are commonly found in familial hypertrophic/dilated cardiomyopathy, and also can cause Laing early-onset distal myopathy (LDM), myosin storage myopathy (MSM), and congenital myopathy with fiber-type disproportion (CFTD). Here we report two cases whose diagnosis was hereditary myopathy according to clinical feature and muscle pathology analysis. High-throughput genomic sequencing (next generation sequencing) was performed to validate the diagnosis. Two MYH7 mutations, p.R1845W and p.E1687del, were identified. p.R1845W was found in a male patient showing weakness of both terminal lower legs without foot drop. Muscle pathology stainings characteristically showed the hyaline body in the intracytoplasmic location. The novel mutation p.E1687del was found in a family with seven patients. The proband showed foot drop, scoliosis, and winged scapula, while his mother only showed mild foot drop and winged scapula. Muscle pathology analysis showed congenital centronucleus myopathy. Both cases only showed muscular disorder and had no cardiomyopathy. This study, for the first time, reports the MYH7 mutations associated with centronucleus myopathy.
KeywordsMYH7 Myopathy Muscle Pathogenesis Next generation sequencing (NGS)
We wish to thank the people with myopathy who participated in this study.
Compliance with ethical standards
The study was approved by the Ethical Committee of the Third Hospital of Hebei Medical University and was conducted in accordance with the Declaration of Helsinki.
Conflict of interest
The authors declare that there is no conflict of interest.
- 4.Naddaf E and Waclawik, Andrew J. (2015) Two Families With MYH7 Distal Myopathy Associated With Cardiomyopathy and Core Formations. J Clin Neuromusc Dis 16(3):164–169 https://doi.org/10.1097/CND.0000000000000069
- 5.Muelas N, Hackman P, Luque H, Garces-Sanchez M, Azorin I, Suominen T, Sevilla T, Mayordomo F, Gomez L, Marti P, Maria Millan J, Udd B, Vilchez JJ (2010) MYH7 gene tail mutation causing myopathic profiles beyond Laing distal myopathy. Neurology 75(8):732–741. https://doi.org/10.1212/WNL.0b013e3181eee4d5 CrossRefPubMedGoogle Scholar
- 7.Laing NG, Ceuterick-de Groote C, Dye DE, Liyanage K, Duff RM, Dubois B, Robberecht W, Sciot R, Martin JJ, Goebel HH (2005) Myosin storage myopathy: slow skeletal myosin (MYH7) mutation in two isolated cases. Neurology 64(3):527–529. https://doi.org/10.1212/01.WNL.0000150581.37514.30 CrossRefPubMedGoogle Scholar
- 12.Oda T, Xiong H, Kobayashi K, Wang S, Satake W, Jiao H, Yang Y, Cha PC, Hayashi YK, Nishino I, Suzuki Y, Sugano S, Wu X, Toda T (2015) A de novo mutation of the MYH7 gene in a large Chinese family with autosomal dominant myopathy. Human Genome Variation 2:15022. https://doi.org/10.1038/hgv.2015.22 CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Clarke NF, Amburgey K, Teener J, Camelo-Piragua S, Kesari A, Punetha J, Waddell LB, Davis M, Laing NG, Monnier N, North KN, Hoffman EP, Dowling JJ (2013) A novel mutation expands the genetic and clinical spectrum of MYH7-related myopathies. Neuromuscul Disord 23(5):432–436. https://doi.org/10.1016/j.nmd.2013.02.009 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Cullup T, Lamont PJ, Cirak S, Damian MS, Wallefeld W, Gooding R, Tan SV, Sheehan J, Muntoni F, Abbs S, Sewry CA, Dubowitz V, Laing NG, Jungbluth H (2012) Mutations in MYH7 cause multi-minicore disease (MmD) with variable cardiac involvement. Neuromuscul Disord 22(12):1096–1104. https://doi.org/10.1016/j.nmd.2012.06.007 CrossRefPubMedGoogle Scholar
- 18.Ortolano S, Tarrío R, Blanco-Arias P, Teijeira S, Rodríguez-Trelles F, García-Murias M, Delague V, Lévy N, Fernández JM, Quintáns B, Millán BS, Carracedo Á, Navarro C, Sobrido MJ (2011) A novel MYH7 mutation links congenital fiber type disproportion and myosin storage myopathy. Neuromuscul Disord 21(4):254–262. https://doi.org/10.1016/j.nmd.2010.12.011 CrossRefPubMedGoogle Scholar
- 21.Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, ACMG Laboratory Quality Assurance Committee (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine 17(5):405–423. https://doi.org/10.1038/gim.2015.30 CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Meredith C, Herrmann R, Parry C, Liyanage K, Dye DE, Durling HJ, Duff RM, Beckman K, de Visser M, van der Graaff MM, Hedera P, Fink JK, Petty EM, Lamont P, Fabian V, Bridges L, Voit T, Mastaglia FL, Laing NG (2004) Mutations in the slow skeletal muscle fiber myosin heavy chain gene (MYH7) cause laing early-onset distal myopathy (MPD1). Am J Hum Genet 75(4):703–708. https://doi.org/10.1086/424760 CrossRefPubMedPubMedCentralGoogle Scholar