Malignant hypertrophic cardiomyopathy caused by the Arg723Gly mutation in beta-myosin heavy chain gene.
Mutations causing hypertrophic cardiomyopathy have been described in nine genes encoding sarcomeric proteins. We report a new mutation in three families, with a C-->G transversion in nucleotide 12 307 of the beta-myosin heavy chain gene, located at the essential light chain interacting region, resulting in the replacement of arginine by glycine at amino acid residue 723. PCR amplification of the selected regions followed by single strand conformation polymorphism analysis, DNA sequencing of the polymorphic patterns and restriction analysis were used to detect the mutation. A total of 23 individuals were diagnosed as carriers, and seven were obligate carriers or had been clinically diagnosed. The Arg723Gly mutation was associated with a malignant phenotype. Ten out of 30 affected members died suddenly or needed an implantable cardioverter-defibrillator at a mean age of 42, and seven members developed progressive heart failure, leading to death or heart transplant in five, at a mean age of 50 years. Echocardiography showed non-obstructive left ventricular hypertrophy in affected members older than 20 (sensitivity 68%). Mean survival of affected members was 51 years. In conclusion, a new mutation Arg723Gly in beta-myosin heavy chain gene is reported which shortens life expectancy because of sudden death and end-stage heart failure.
Enjuto
M
M
Molecular Cardiology Laboratory, Laboratory of Clinical Biochemistry and the Cardiovascular Institute, Hospital Clinic (IDIBAPS), University of Barcelona, Villarroel 170, Barcelona, 08036, Spain.
Francino
A
A
Navarro-López
F
F
Viles
D
D
Paré
J C
JC
Ballesta
A M
AM
D000328:Adult; D000367:Age Factors; D000368:Aged; D001120:Arginine / Q000737:chemistry*; D009202:Cardiomyopathies / Q000235:genetics* / Q000401:mortality; D004562:Electrocardiography; D005260:Female; D005998:Glycine / Q000737:chemistry*; D006801:Humans; D008017:Life Expectancy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA
D001120:Arginine; D018995:Myosin Heavy Chains; D005998:Glycine