CLINICAL RESEARCH
Comprehensive analysis of the beta-myosin heavy chain gene in 389 unrelated patients with hypertrophic cardiomyopathy
Sara L. Van Driest, BA*,
Michele A. Jaeger, BA*,
Steve R. Ommen, MD, FACC ,
Melissa L. Will, BS*,
Bernard J. Gersh, MD, FACC,
A. Jamil Tajik, MD, FACC and
Michael J. Ackerman, MD, PhD, FACC*,*
* Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
Department of Internal Medicine/Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
Department of Pediatric and Adolescent Medicine/Division of Pediatric Cardiology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
Manuscript received November 4, 2003;
revised manuscript received March 18, 2004,
accepted April 13, 2004.
* Reprint requests and correspondence: Dr. Michael J. Ackerman, Sudden Death Genomics Laboratory, Guggenheim 501, Mayo Clinic, Rochester, Minnesota 55905, USA.
ackerman.michael{at}mayo.edu
OBJECTIVES: We sought to determine the prevalence and phenotype of beta-myosin heavy chain gene MYH7 mutations in a large cohort of unrelated patients with hypertrophic cardiomyopathy (HCM).
BACKGROUND: Hypertrophic cardiomyopathy is a heterogeneous cardiac disease. MYH7 mutations are one of the most common genetic causes of HCM and have been associated with severe hypertrophy, young age of diagnosis, and high risk of sudden cardiac death. However, these clinical findings from large, family studies have not been confirmed in a large unrelated cohort.
METHODS: Deoxyribonucleic (DNA) samples obtained from 389 HCM outpatients seen at this tertiary referral center were analyzed for mutations, using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing for all 38 protein-coding exons of MYH7. Clinical data were extracted from patient records blinded to patient genotype.
RESULTS: Fifty-eight patients (15%) harbored 40 different mutations in MYH7. Compared with HCM patients without MYH7 mutations, HCM patients with MYH7 were younger at diagnosis (32.9 vs. 42.7 years, p = 0.0002), had more hypertrophy (left ventricular wall thickness of 24.2 vs. 21.1 mm, p = 0.0009), and more frequently underwent myectomy (60% vs. 38%, p = 0.002). The HCM patients with MYH7 mutations more often had a family history of HCM (43% vs. 29%, p = 0.006), but there was no difference in family history of sudden death (16% vs. 14%, p = NS).
CONCLUSIONS: In this setting, HCM patients with MYH7 were diagnosed at a younger age and had more hypertrophy, but they had no greater frequency of sudden death among first-degree relatives. Although these associations may prove useful for targeted gene screening, caution should be exercised in terms of using pathogenic status in risk stratification.
|
Abbreviations and Acronyms
| | DHPLC | = denaturing high-performance liquid chromatography | | HCM | = hypertrophic cardiomyopathy | | ICD | = implantable cardioverter-defibrillator | | LVWT | = left ventricular wall thickness | | MYH7 | = beta-myosin heavy chain gene | | PCR | = polymerase chain reaction | | SCD | = sudden cardiac death | | SNP | = single-nucleotide polymorphism |
|
This article has been cited by other articles:
|
|
|
|
 
M. Michels, O. I.I. Soliman, M. J. Kofflard, Y. M. Hoedemaekers, D. Dooijes, D. Majoor-Krakauer, and F. J. ten Cate
Diastolic abnormalities as the first feature of hypertrophic cardiomyopathy in Dutch myosin-binding protein C founder mutations.
J. Am. Coll. Cardiol. Img.,
January 1, 2009;
2(1):
58 - 64.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Penicka, P. Gregor, R. Kerekes, D. Marek, K. Curila, J. Krupicka, and for the Candesartan use in Hypertrophic And Non-ob
The Effects of Candesartan on Left Ventricular Hypertrophy and Function in Nonobstructive Hypertrophic Cardiomyopathy: A Pilot, Randomized Study
J. Mol. Diagn.,
January 1, 2009;
11(1):
35 - 41.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Jacques, N. Briceno, A. E. Messer, C. E. Gallon, S. Jalilzadeh, E. Garcia, G. Kikonda-Kanda, J. Goddard, S. E. Harding, H. Watkins, et al.
The molecular phenotype of human cardiac myosin associated with hypertrophic obstructive cardiomyopathy
Cardiovasc Res,
August 1, 2008;
79(3):
481 - 491.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Olivotto, F. Girolami, M. J. Ackerman, S. Nistri, J. M. Bos, E. Zachara, S. R. Ommen, J. L. Theis, R. A. Vaubel, F. Re, et al.
Myofilament Protein Gene Mutation Screening and Outcome of Patients With Hypertrophic Cardiomyopathy
Mayo Clin. Proc.,
June 1, 2008;
83(6):
630 - 638.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Morita, H. L. Rehm, A. Menesses, B. McDonough, A. E. Roberts, R. Kucherlapati, J. A. Towbin, J.G. Seidman, and C. E. Seidman
Shared Genetic Causes of Cardiac Hypertrophy in Children and Adults
N. Engl. J. Med.,
May 1, 2008;
358(18):
1899 - 1908.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Revera, L. van der Merwe, M. Heradien, A. Goosen, V. A. Corfield, P. A. Brink, and J. C. Moolman-Smook
Troponin T and {beta}-myosin mutations have distinct cardiac functional effects in hypertrophic cardiomyopathy patients without hypertrophy
Cardiovasc Res,
March 1, 2008;
77(4):
687 - 694.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Medin, M. Hermida-Prieto, L. Monserrat, R. Laredo, J. C. Rodriguez-Rey, X. Fernandez, and A. Castro-Beiras
Mutational screening of phospholamban gene in hypertrophic and idiopathic dilated cardiomyopathy and functional study of the PLN -42 C>G mutation
Eur J Heart Fail,
January 1, 2007;
9(1):
37 - 43.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Richard, E. Villard, P. Charron, and R. Isnard
The Genetic Bases of Cardiomyopathies
J. Am. Coll. Cardiol.,
October 27, 2006;
48(9_Suppl_A):
A79 - A89.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Binder, S. R. Ommen, B. J. Gersh, S. L. Van Driest, A. J. Tajik, R. A. Nishimura, and M. J. Ackerman
Echocardiography-Guided Genetic Testing in Hypertrophic Cardiomyopathy: Septal Morphological Features Predict the Presence of Myofilament Mutations
Mayo Clin. Proc.,
April 1, 2006;
81(4):
459 - 467.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Perkins, S. L. Van Driest, E. G. Ellsworth, M. L. Will, B. J. Gersh, S. R. Ommen, and M. J. Ackerman
Gene-specific modifying effects of pro-LVH polymorphisms involving the renin-angiotensin-aldosterone system among 389 unrelated patients with hypertrophic cardiomyopathy
Eur. Heart J.,
November 2, 2005;
26(22):
2457 - 2462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Ackerman, S. L. Van Driest, and M. Bos
Are Longitudinal, Natural History Studies the Next Step in Genotype-Phenotype Translational Genomics in Hypertrophic Cardiomyopathy?
J. Am. Coll. Cardiol.,
November 1, 2005;
46(9):
1744 - 1746.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. Van Driest, S. R. Ommen, A. J. Tajik, B. J. Gersh, and M. J. Ackerman
Yield of Genetic Testing in Hypertrophic Cardiomyopathy
Mayo Clin. Proc.,
June 1, 2005;
80(6):
739 - 744.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. L. Van Driest, S. R. Ommen, A. J. Tajik, B. J. Gersh, and M. J. Ackerman
Sarcomeric Genotyping in Hypertrophic Cardiomyopathy
Mayo Clin. Proc.,
April 1, 2005;
80(4):
463 - 469.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. L. Van Driest, V. C. Vasile, S. R. Ommen, M. L. Will, A. J. Tajik, B. J. Gersh, and M. J. Ackerman
Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy
J. Am. Coll. Cardiol.,
November 2, 2004;
44(9):
1903 - 1910.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
