A double heterozygous variant in MYH6 and MYH7 associated with hypertrophic cardiomyopathy in a Japanese Family

Published:October 20, 2021DOI:https://doi.org/10.1016/j.jccase.2021.09.011

      Abstract

      Hypertrophic cardiomyopathy (HCM) is genetically heterogeneous. Different variants associated with HCM have been identified in several cardiac sarcomeric protein genes. We identified the heterozygous missense variant c.2191 C>A p. Pro 731 Thr in the MYH7 gene and the heterozygous frameshift variant c.1091–1092 insTGAA p.Lys364fs*in the MYH6 gene in a Japanese family. Family members with the double variants demonstrated severe phenotypes, such as sudden cardiac-related death and heart failure. These double variants were well segregated and might be responsible for the severity of cardiovascular events in affected family members. These double variants are potentially associated with specific phenotypes in HCM. Further studies are needed to analyze specific gene functions.

      Keywords

      To read this article in full you will need to make a payment

      References

        • Maron B.J.
        • Rowin E.J.
        • Maron M.S.
        Paradigm of sudden death prevention in hypertrophic cardiomyopathy.
        Circ Res. 2019; 125: 370-378
        • Semsarian C.
        • Ingles J.
        • Maron M.S.
        • Maron B.J.
        New perspectives on the prevalence of hypertrophic cardiomyopathy.
        J Am Coll Cardiol. 2015; 65: 1249-1254
        • Mathew J.
        • Zahavich L.
        • Lafreniere-Roula M.
        • Wilson J.
        • George K.
        • Benson L.
        • Bowdin S.
        • Mital S.
        Utility of genetics for risk stratification in pediatric hypertrophic cardiomyopathy.
        Clin Genet. 2018; 93: 310-319
        • Wang C.
        • Hata Y.
        • Hirono K.
        • Takasaki A.
        • Ozawa S.W.
        • Nakaoka H.
        • Saito K.
        • Miyao N.
        • Okabe M.
        • Ibuki K.
        • Nishida N.
        • Origasa H.
        • Yu X.
        • Bowles N.E.
        • Ichida F.
        A wide and specific spectrum of genetic variants and genotype-phenotype correlations revealed by next-generation sequencing in patients with left ventricular noncompaction.
        J Am Heart Assoc. 2017; 6 (e006210)
        • Richards S.
        • Aziz N.
        • Bale S.
        • Bick D.
        • Das S.
        • Gastier-Foster J.
        • Grody W.W.
        • Hegde M.
        • Lyon E.
        • Spector E.
        • Voelkerding K.
        • Rehm H.L.
        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.
        Genet Med. 2015; 17: 405-424
        • Marsiglia J.D.C.
        • Credidio F.L.
        • de Oliveira T.G.M.
        • Reis R.F.
        • Antunes M de O.
        • de Araujo A.Q.
        • Pedrosa R.P.
        • Barbosa-Ferreira J.M.B.
        • Mady C.
        • Krieger J.E.
        • Arteaga-Fernandez E.
        • da Costa Pereira A.
        Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy.
        Am Heart J. 2013; 166: 775-782
        • Niimura H.
        • Patton K.K.
        • McKenna W.J.
        • Soults J.
        • Maron B.J.
        • Seidman J.G.
        • et al.
        Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly.
        Circulation. 2002; 105: 446-451
        • Carniel E.
        • Taylor M.R.G.
        • Sinagra G.
        • Di Lenarda A.
        • Ku L.
        • Fain P.R.
        • et al.
        Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and hypertrophic phenotypes of cardiomyopathy.
        Circulation. 2005; 112: 54-59
        • Burns C.
        • Bagnall R.D.
        • Lam L.
        • Semsarian C.
        • Ingles J.
        Multiple gene variants in hypertrophic cardiomyopathy in the era of next-generation sequencing.
        Circ Cardiovasc Genet. 2017; 10 (e001666)
        • Miron A.
        • Lafreniere-Roula M.
        • Steve Fan C.-.P.
        • Armstrong K.R.
        • Dragulescu A.
        • Papaz T.
        • et al.
        A validated model for sudden cardiac death risk prediction in pediatric hypertrophic cardiomyopathy.
        Circulation. 2020; 142: 217-229