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Updated: Aug 17, 2026
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Yield of genetic testing in hypertrophic cardiomyopathy
Sara L Van Driest1, Steve R Ommen, A Jamil Tajik
1Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Insights
Younger age, family history of hypertrophic cardiomyopathy (HCM), and increased left ventricular wall thickness significantly predict sarcomeric mutations. These clinical factors can guide genetic testing for HCM patients.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
Background:
- Hypertrophic cardiomyopathy (HCM) is a primary genetic heart muscle disease.
- Identifying the underlying genetic cause is crucial for diagnosis and management.
Purpose of the Study:
- To identify clinical parameters in hypertrophic cardiomyopathy (HCM) patients that correlate with the presence of sarcomeric mutations.
- To improve the diagnostic yield of genetic testing in HCM.
Main Methods:
- Comprehensive mutational analysis of 8 sarcomeric genes in 389 unrelated HCM patients.
- Clinical data extraction and blinded genotype analysis.
- Statistical correlation of clinical parameters with sarcomeric mutation presence.
Main Results:
- Younger age at diagnosis, family history of HCM, and increased left ventricular wall thickness were significantly associated with identifying sarcomeric mutations.
- Family history of sudden cardiac death, myectomy status, and anatomical subtype did not show significant correlation.
- A scoring system based on age, wall thickness, and family history could estimate mutation likelihood.
Conclusions:
- Clinical predictors like age, left ventricular hypertrophy, and family history of HCM aid in selecting patients for genetic testing.
- Utilizing these predictors can enhance the efficiency of cardiac sarcomere gene screening.
Objective:
To determine the clinical parameters of hypertrophic cardiomyopathy (HCM) that correlated significantly with the presence of an identifiable sarcomeric mutation.
Patients And Methods:
Previous comprehensive mutational analyses of all protein-coding exons of 8 sarcomeric genes revealed pathogenic mutations in 147 (38%) of 389 unrelated patients seen at the HCM outpatient clinic at the Mayo Clinic in Rochester, Minn, between April 1997 and December 2001. Clinical data, extracted from patient records and blinded to patient genotype, were maintained in a custom database.
Results:
In 389 unrelated patients, younger age at diagnosis, family history of HCM, and Increasing left ventricular wall thickness were all associated with Increased likelihood of identifying an HCM-associated sarcomeric mutation. In contrast, family history of sudden cardiac death, myectomy status, and anatomical subtype did not correlate significantly with genotype-positive status. With use of a simple scoring system based on age at diagnosis, left ventricular wall thickness, and family history of HCM, the likelihood of a sarcomeric mutation could be estimated.
Conclusion:
Clinical predictors of positive genotype, such as the presence of an implantable cardioverter-defibrillator, age at diagnosis, degree of left ventricular wall hypertrophy, and family history of HCM, may aid in patient selection for genetic testing and increase the yield of cardiac sarcomere gene screening.
