Skip to main content
Journal cover image

Familial hypertrophic cardiomyopathy and atrial fibrillation caused by Arg663His beta-cardiac myosin heavy chain mutation.

Publication ,  Journal Article
Gruver, EJ; Fatkin, D; Dodds, GA; Kisslo, J; Maron, BJ; Seidman, JG; Seidman, CE
Published in: Am J Cardiol
June 17, 1999

More than 40 different beta-cardiac myosin heavy chain (beta-MHC) missense mutations have been identified that cause familial hypertrophic cardiomyopathy (FHC). Some of these are recognized to have important clinical manifestations, such as an increased incidence of sudden death. We report that the beta-MHC missense mutation Arg663His causes predominant cardiac morphology and atrial fibrillation. Longitudinal clinical evaluations were performed in a kindred with FHC. The nucleotide sequence of the beta-MHC gene was analyzed to define the causal mutation. A missense mutation in the beta-MHC gene, Arg663His, was identified in 24 individuals. Clinical studies demonstrated modest left ventricular hypertrophy in affected individuals, predominantly localized in the proximal segment of the interventricular septum, which increased (average = 40 +/- 8%) during 7 years of follow-up. Results showed that 47% of Arg663His adults (age > 16 years) with ventricular hypertrophy developed atrial fibrillation, significantly more (p <0.001) than observed in ungenotyped FHC populations. Survival of affected individuals remained near normal. The beta-MHC missense mutation Arg663His causes a characteristic pattern of ventricular hypertrophy. Arg663His individuals have a markedly higher prevalence of atrial fibrillation, compared with a population with ungenotyped hypertrophic cardiomyopathy. The demonstration of phenotype as a direct consequence of genotype further extends the utility of molecular data in clinical medicine. Early identification of Arg663His individuals has the potential to minimize the serious sequelae of this arrhythmia in this FHC group.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Am J Cardiol

DOI

ISSN

0002-9149

Publication Date

June 17, 1999

Volume

83

Issue

12A

Start / End Page

13H / 18H

Location

United States

Related Subject Headings

  • Retrospective Studies
  • Prognosis
  • Pedigree
  • Myosin Heavy Chains
  • Mutation, Missense
  • Molecular Sequence Data
  • Middle Aged
  • Male
  • Humans
  • Genotype
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gruver, E. J., Fatkin, D., Dodds, G. A., Kisslo, J., Maron, B. J., Seidman, J. G., & Seidman, C. E. (1999). Familial hypertrophic cardiomyopathy and atrial fibrillation caused by Arg663His beta-cardiac myosin heavy chain mutation. Am J Cardiol, 83(12A), 13H-18H. https://doi.org/10.1016/s0002-9149(99)00251-9
Gruver, E. J., D. Fatkin, G. A. Dodds, J. Kisslo, B. J. Maron, J. G. Seidman, and C. E. Seidman. “Familial hypertrophic cardiomyopathy and atrial fibrillation caused by Arg663His beta-cardiac myosin heavy chain mutation.Am J Cardiol 83, no. 12A (June 17, 1999): 13H-18H. https://doi.org/10.1016/s0002-9149(99)00251-9.
Gruver EJ, Fatkin D, Dodds GA, Kisslo J, Maron BJ, Seidman JG, et al. Familial hypertrophic cardiomyopathy and atrial fibrillation caused by Arg663His beta-cardiac myosin heavy chain mutation. Am J Cardiol. 1999 Jun 17;83(12A):13H-18H.
Gruver, E. J., et al. “Familial hypertrophic cardiomyopathy and atrial fibrillation caused by Arg663His beta-cardiac myosin heavy chain mutation.Am J Cardiol, vol. 83, no. 12A, June 1999, pp. 13H-18H. Pubmed, doi:10.1016/s0002-9149(99)00251-9.
Gruver EJ, Fatkin D, Dodds GA, Kisslo J, Maron BJ, Seidman JG, Seidman CE. Familial hypertrophic cardiomyopathy and atrial fibrillation caused by Arg663His beta-cardiac myosin heavy chain mutation. Am J Cardiol. 1999 Jun 17;83(12A):13H-18H.
Journal cover image

Published In

Am J Cardiol

DOI

ISSN

0002-9149

Publication Date

June 17, 1999

Volume

83

Issue

12A

Start / End Page

13H / 18H

Location

United States

Related Subject Headings

  • Retrospective Studies
  • Prognosis
  • Pedigree
  • Myosin Heavy Chains
  • Mutation, Missense
  • Molecular Sequence Data
  • Middle Aged
  • Male
  • Humans
  • Genotype