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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2017

Open Access 01-12-2017 | Case report

Novel phenotypic variant in the MYH7 spectrum due to a stop-loss mutation in the C-terminal region: a case report

Authors: Zsolt Bánfai, Kinga Hadzsiev, Endre Pál, Katalin Komlósi, Márton Melegh, László Balikó, Béla Melegh

Published in: BMC Medical Genetics | Issue 1/2017

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Abstract

Background

Defects of the slow myosin heavy chain isoform coding MYH7 gene primarily cause skeletal myopathies including Laing Distal Myopathy, Myosin Storage Myopathy and are also responsible for cardiomyopathies. Scapuloperoneal and limb-girdle muscle weakness, congenital fiber type disproportion, multi-minicore disease were also reported in connection of MYH7. Pathogeneses of the defects in the head and proximal rod region of the protein are well described. However, the C-terminal mutations of the MYH7 gene are less known. Moreover, only two articles describe the phenotypic impact of the elongated mature protein product caused by termination signal loss.

Case presentation

Here we present a male patient with an unusual phenotypic variant of early-onset and predominant involvement of neck muscles with muscle biopsy indicating myopathy and sarcoplasmic storage material. Cardiomyopathic involvements could not be observed. Sequencing of MYH7 gene revealed a stop-loss mutation on the 3-prime end of the rod region, which causes the elongation of the mature protein.

Conclusions

The elongated protein likely disrupts the functions of the sarcomere by multiple functional abnormalities. This elongation could also affect the thick filament degradation leading to protein deposition and accumulation in the sarcomere, resulting in the severe myopathy of certain axial muscles. The phenotypic expression of the detected novel MYH7 genotype could strengthen and further expand our knowledge about mutations affecting the structure of MyHCI by termination signal loss in the MYH7 gene.
Literature
1.
Scott W, Stevens J, Binder-Macleod SA. Human skeletal muscle fiber type classifications. Phys Ther. 2001;81(11):1810–6.PubMed
2.
Pette D, Staron RS. Myosin isoforms, muscle fiber types, and transitions. Microsc Res Tech. 2000;50(6):500–9.CrossRefPubMed
3.
4.
Atkinson SJ, Stewart M. Molecular basis of myosin assembly: coiled-coil interactions and the role of charge periodicities. J Cell Sci Suppl. 1991;14:7–10.CrossRefPubMed
5.
Atkinson SJ, Stewart M. Molecular interactions in myosin assembly. Role of the 28-residue charge repeat in the rod. J Mol Biol. 1992;226(1):7–13.CrossRefPubMed
6.
Armel TZ, Leinwand LA. Mutations in the beta-myosin rod cause myosin storage myopathy via multiple mechanisms. Proc Natl Acad Sci U S A. 2009;106(15):6291–6.CrossRefPubMedPubMedCentral
7.
Feinstein-Linial M, Buvoli M, Buvoli A, Sadeh M, Dabby R, Straussberg R, Shelef I, Dayan D, Leinwand LA, Birk OS. Two novel MYH7 proline substitutions cause Laing distal Myopathy-like phenotypes with variable expressivity and neck extensor contracture. BMC Med Genet. 2016;17(1):57.CrossRefPubMedPubMedCentral
8.
Komlosi K, Hadzsiev K, Garbes L, Martinez Carrera LA, Pal E, Sigurethsson JH, Magnusson O, Melegh B, Wirth B. Exome sequencing identifies Laing distal myopathy MYH7 mutation in a Roma family previously diagnosed with distal neuronopathy. Neuromuscular disorders: NMD. 2014;24(2):156–61.CrossRefPubMed
9.
10.
Stalpers X, Verrips A, Braakhekke J, Lammens M, van den Wijngaard A, Mostert A. Scoliosis surgery in a patient with “de novo” myosin storage myopathy. Neuromuscular disorders: NMD. 2011;21(11):812–5.CrossRefPubMed
11.
Tajsharghi H, Thornell LE, Lindberg C, Lindvall B, Henriksson KG, Oldfors A. Myosin storage myopathy associated with a heterozygous missense mutation in MYH7. Ann Neurol. 2003;54(4):494–500.CrossRefPubMed
12.
Shingde MV, Spring PJ, Maxwell A, Wills EJ, Harper CG, Dye DE, Laing NG, North KN. Myosin storage (hyaline body) myopathy: a case report. Neuromuscular disorders: NMD. 2006;16(12):882–6.CrossRefPubMed
13.
Tajsharghi H, Oldfors A, Macleod DP, Swash M. Homozygous mutation in MYH7 in myosin storage myopathy and cardiomyopathy. Neurology. 2007;68(12):962.CrossRefPubMed
14.
Bohlega S, Abu-Amero SN, Wakil SM, Carroll P, Al-Amr R, Lach B, Al-Sayed Y, Cupler EJ, Meyer BF. Mutation of the slow myosin heavy chain rod domain underlies hyaline body myopathy. Neurology. 2004;62(9):1518–21.CrossRefPubMed
15.
Sohn RL, Vikstrom KL, Strauss M, Cohen C, Szent-Gyorgyi AG, Leinwand LA. A 29 residue region of the sarcomeric myosin rod is necessary for filament formation. J Mol Biol. 1997;266(2):317–30.CrossRefPubMed
16.
Cohen C, Parry DA. A conserved C-terminal assembly region in paramyosin and myosin rods. J Struct Biol. 1998;122(1–2):180–7.CrossRefPubMed
17.
Ortolano S, Tarrio R, Blanco-Arias P, Teijeira S, Rodriguez-Trelles F, Garcia-Murias M, Delague V, Levy N, Fernandez JM, Quintans B, et al. A novel MYH7 mutation links congenital fiber type disproportion and myosin storage myopathy. Neuromuscular disorders: NMD. 2011;21(4):254–62.CrossRefPubMed
18.
Fiorillo C, Astrea G, Savarese M, Cassandrini D, Brisca G, Trucco F, Pedemonte M, Trovato R, Ruggiero L, Vercelli L, et al. MYH7-Related myopathies: clinical, histopathological and imaging findings in a cohort of Italian patients. Orphanet journal of rare diseases. 2016;11(1):91.CrossRefPubMedPubMedCentral
19.
Meredith C, Herrmann R, Parry C, Liyanage K, Dye DE, Durling HJ, Duff RM, Beckman K, de Visser M, van der Graaff MM, et al. Mutations in the slow skeletal muscle fiber myosin heavy chain gene (MYH7) cause laing early-onset distal myopathy (MPD1). Am J Hum Genet. 2004;75(4):703–8.CrossRefPubMedPubMedCentral
20.
Darin N, Tajsharghi H, Ostman-Smith I, Gilljam T, Oldfors A. New skeletal myopathy and cardiomyopathy associated with a missense mutation in MYH7. Neurology. 2007;68(23):2041–2.CrossRefPubMed
21.
Schwarz JM, Cooper DN, Schuelke M, Seelow D. MutationTaster2: Mutation prediction for the deep-sequencing age. Nat Methods. 2014;11(4):361–2.CrossRefPubMed
22.
Reva B, Antipin Y, Sander C. Predicting the functional impact of protein mutations: application to cancer genomics. Nucleic Acids Res. 2011;39(17):e118.CrossRefPubMedPubMedCentral
23.
24.
Desmet FO, Hamroun D, Lalande M, Collod-Beroud G, Claustres M, Beroud C. Human splicing finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res. 2009;37(9):e67.CrossRefPubMedPubMedCentral
25.
McDonnell AV, Jiang T, Keating AE, Berger B. Paircoil2: Improved prediction of coiled coils from sequence. Bioinformatics. 2006;22(3):356–8.CrossRefPubMed
26.
Kircher M, Witten DM, Jain P, O'Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014;46(3):310–5.CrossRefPubMedPubMedCentral
27.
Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2001;29(1):308–11.CrossRefPubMedPubMedCentral
28.
Landrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Hoover J, et al. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res. 2016;44(D1):D862–8.CrossRefPubMed
29.
Stenson PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS, Abeysinghe S, Krawczak M, Cooper DN. Human gene mutation database (HGMD): 2003 update. Hum Mutat. 2003;21(6):577–81.CrossRefPubMed
30.
Fokkema IFAC, Taschner PEM, Schaafsma GCP, Celli J, Laros JFJ, den Dunnen JT. LOVD v.2.0: The next generation in gene variant databases. Hum Mutat. 2011;32(5):557–63.CrossRefPubMed
31.
Hebsgaard SM, Korning PG, Tolstrup N, Engelbrecht J, Rouze P, Brunak S. Splice site prediction in Arabidopsis Thaliana pre-mRNA by combining local and global sequence information. Nucleic Acids Res. 1996;24(17):3439–52.CrossRefPubMedPubMedCentral
32.
Brunak S, Engelbrecht J, Knudsen S. Prediction of human mRNA donor and acceptor sites from the DNA sequence. J Mol Biol. 1991;220(1):49–65.CrossRefPubMed
33.
Martin AF, Bhatti S, Pyne-Geithman GJ, Farjah M, Manaves V, Walker L, Franks R, Strauch AR, Paul RJ. Expression and function of COOH-terminal myosin heavy chain isoforms in mouse smooth muscle. American journal of physiology Cell physiology. 2007;293(1):C238–45.CrossRefPubMed
34.
Lupas A, Van Dyke M, Stock J. Predicting coiled coils from protein sequences. Science. 1991;252(5009):1162–4.CrossRefPubMed
35.
O'Neil KT, DeGrado WF. A thermodynamic scale for the helix-forming tendencies of the commonly occurring amino acids. Science. 1990;250(4981):646–51.CrossRefPubMed
Metadata
Title
Novel phenotypic variant in the MYH7 spectrum due to a stop-loss mutation in the C-terminal region: a case report
Authors
Zsolt Bánfai
Kinga Hadzsiev
Endre Pál
Katalin Komlósi
Márton Melegh
László Balikó
Béla Melegh
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2017
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-017-0463-y

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