Pediatric restrictive cardiomyopathy associated with a mutation in β-myosin heavy chain

• Published in: Clinical genetics Vol. 73; no. 2; pp. 165 - 170
• Main Authors: Ware, SM, Quinn, ME, Ballard, ET, Miller, E, Uzark, K, Spicer, RL
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2008; Blackwell
• Subjects: Adult; Amino Acid Sequence; Biological and medical sciences; cardiac transplantation; Cardiology. Vascular system; Cardiomyopathies - genetics; Cardiomyopathies - surgery; Fundamental and applied biological sciences. Psychology; gene mutation; General aspects. Genetic counseling; Genetics of eukaryotes. Biological and molecular evolution; Heart; Heart Murmurs - diagnosis; Heart Transplantation; Humans; Infant; Male; Medical genetics; Medical sciences; Molecular and cellular biology; Molecular Sequence Data; Myocarditis. Cardiomyopathies; Myosin Heavy Chains - genetics; restrictive cardiomyopathy; sarcomere; Sequence Alignment; Ventricular Myosins - genetics; β-myosin heavy chain; Human; Heart; β-myosin heavy chain; Heavy peptide chain; gene mutation; Beta-Peptide chain; cardiac transplantation; Restrictive cardiomyopathy; Cardiovascular disease; Transplantation; Homotransplantation; Myocardial disease; sarcomere; Association; Treatment; Gene; Heart disease; Surgery; Myosin; Graft; Genetics; Mutation; Child; Constrictive hypertrophic cardiomyopathy
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2007.00939.x

Most children do not have a known cause of cardiomyopathy which limits the potential for disease‐specific therapies. Of the different phenotypic presentations of cardiomyopathy, the restrictive form carries the poorest prognosis and has the lowest rate of identification of etiology. We present the first description of a β‐myosin heavy chain gene mutation in an infant with restrictive cardiomyopathy requiring cardiac transplantation. As demonstrated by three‐dimensional protein structure modeling, the missense mutation is in a highly conserved amino acid at the critical binding region for the essential light chain. This case emphasizes that mutations in sarcomeric proteins, which are known to cause hypertrophic cardiomyopathy in adults, may be associated with the development of restrictive physiology in childhood. Identification of the genetic basis of pediatric cardiomyopathy has important implications for management and genetic counseling.