Advertisement

Successful pregnancy and delivery in a young-onset hypertrophic cardiomyopathy patient with a novel doublet-base substitution in the MYH7 gene

Published:October 01, 2022DOI:https://doi.org/10.1016/j.jccase.2022.09.010

      Abstract

      Herein, we report the case of a young-onset female hypertrophic cardiomyopathy (HCM) patient with severe left ventricular outflow tract obstruction who had a family history of premature sudden cardiac death. Despite the severe HCM phenotype, the patient was successfully managed by low-dose bisoprolol during two peripartum periods after a percutaneous transluminal septal myocardial ablation.
      We performed whole-genome sequencing analysis and found a novel doublet-base substitution (DBS) in the MYH7 gene (c.2608_2609delinsTT, p.R870F) in this patient. Her children were also genetically tested after careful genetic counselling to their parents, and one of her children at 1-year-old with left ventricular hypertrophy was found to have the same gene mutation. The location of the DBS in a functionally important domain and the inheritance of the same mutation in the offspring with the HCM phenotype suggested that this mutation in the MYH7 gene was responsible for the severe HCM phenotype. Proactive genetic testing would provide beneficial information for appropriate follow-up and initiation of therapy in children with possibly pathogenic gene mutations; however, revisions of genetic counselling may be considered according to their growth.

      Learning objective

      Hypertrophic cardiomyopathy (HCM) patients with severe left ventricular outflow tract obstruction are at a high risk of hemodynamic deterioration during pregnancy. Preceding myocardial ablation therapy and a careful medical management during peripartum period may enable safe pregnancy and delivery in severe obstructive HCM patients. A novel doublet-base substitution in the MYH7 gene (c.2608_2609delinsTT, p.R870F) was found as a likely pathogenic mutation of young-onset severe HCM.

      Keywords

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

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Cardiology Cases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Maron B.J.
        • Ommen S.R.
        • Semsarian C.
        • Spirito P.
        • Olivotto I.
        • Maron M.S.
        Hypertrophic cardiomyopathy: present and future, with translation into contemporary cardiomyopathy cardiovascular medicine.
        J Am Coll Cardiol. 2014; 64: 83-99
        • Richard P.
        • Charron P.
        • Carrier L.
        • Ledeuil C.
        • Cheav T.
        • Pichereau C.
        • Benaiche A.
        • Isnard R.
        • Dubourg O.
        • Burban M.
        • Gueffet J.P.
        • Millaire A.
        • Desnos M.
        • Schwartz K.
        • Hainque B.
        • et al.
        Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy.
        Circulation. 2003; 107: 2227-2232
        • Li H.
        • Durbin R.
        Fast and accurate short read alignment with burrows-wheeler transform.
        Bioinformatics. 2009; 25: 1754-1760
        • DePristo M.A.
        • Banks E.
        • Poplin R.
        • Garimella K.V.
        • Maguire J.R.
        • Hartl C.
        • Philippakis A.A.
        • del Angel G.
        • Rivas M.A.
        • Hanna M.
        • McKenna A.
        • Fennell T.J.
        • Kernytsky A.M.
        • Sivachenko A.Y.
        • Cibulskis K.
        • et al.
        A framework for variation discovery and genotyping using next-generation DNA sequencing data.
        Nat Genet. 2011; 43: 491-498
        • Veselka J.
        • Anavekar N.S.
        • Charron P.
        Hypertrophic obstructive cardiomyopathy.
        Lancet. 2017; 385: 1253-1267
        • Woo A.
        • Rakowski H.
        • Liew J.C.
        • Zhao M.S.
        • Liew C.C.
        • Parker T.G.
        • Wigle E.D.
        • Zeller M.
        Mutations of the β myosin heavy chain gene in hypertrophic cardiomyopathy: critical functional sites determine prognosis.
        Heart. 2003; 89: 1179-1185
        • Nishi H.
        • Kimura A.
        • Harada H.
        • Koga Y.
        • Adachi K.
        • Matsuyama K.
        • Yasunaga S.
        • Imaizumi T.
        • Toshima H.
        • Sasazuki T.
        • Koyanagi T.
        A myosin missense mutation, not a null allele, causes familial hypertrophic cardiomyopathy.
        Circulation. 1995; 91: 2911-2915
        • Redwood C.S.
        • Moolman-Smook J.C.
        • Watkins H.
        Properties of mutant contractile proteins that cause hypertrophic cardiomyopathy.
        Cardiovasc Res. 1999; 44: 20-36
        • 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.
        ACMG laboratory quality assurance committee. 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
        • Zamorano J.
        • Anastasakis A.
        • Borger M.A.
        • Borggrefe M.
        • Cecchi F.
        • Charron P.
        • Hagege A.
        • Lafont A.
        • Limongelli G.
        • Mahrholdt H.
        • McKenna W.J.
        • Mogensen J.
        • Nihoyannopoulos P.
        • Nistri S.
        • Piepe P.G.
        • et al.
        2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: the task force for the diagnosis and Management of Hypertrophic Cardiomyopathy of the european Society of Cardiology (ESC).
        Eur Heart J. 2014; 35: 2733-2779