Expression of a missense mutation in the messenger RNA for β-myosin heavy chain in myocardial tissue in hypertrophic cardiomyopathy

• Published in: The Journal of clinical investigation 1992-07, Vol.90 (1), p.271-277
• Main Authors: PERRYMAN, M. B, QUN-TAO YU, MARIAN, A. J, MARES, A. JR, CZERNUSZEWICZ, G, IFEGWU, J, HILL, R, ROBERTS, R
• Format: Article
• Language: English
• Subjects: Base Sequence; Biological and medical sciences; Cardiology. Vascular system; Cardiomyopathy, Hypertrophic - genetics; Heart; Humans; Medical sciences; Molecular Sequence Data; Mutation; Myocardium - metabolism; Myosins - genetics; Polymerase Chain Reaction; RNA, Messenger - genetics
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI115848

We have determined that a missense mutation in exon 13 of the beta-myosin heavy chain (beta MHC) gene is expressed in the messenger RNA (mRNA) isolated from a right ventricular endomyocardial biopsy obtained from the proband of a family with hypertrophic cardiomyopathy. The mutation is the result of a substitution of an adenine for a guanine residue in one allele of the beta MHC gene and creates a second recognition site for the restriction endonuclease Ddel in exon 13. The mutation is inherited in a Mendelian fashion and co-segregates with hypertrophic cardiomyopathy in this family. Complementary DNAs synthesized from RNA isolated from the endomyocardial biopsy were cloned into a plasmid vector and sequenced to confirm the expression of both the normal and mutant allele in mRNA of myocardial tissue. This is the first report of the transcription of a mutant beta MHC gene allele into mRNA of the myocardium.