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Evaluation of the Mayo Clinic Phenotype-Based Genotype Predictor Score in Patients with Clinically Diagnosed Hypertrophic Cardiomyopathy

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Abstract

Genetic testing for hypertrophic cardiomyopathy (HCM) can provide an important clinical marker for disease outcome and family screening. This study set out to validate our recently developed phenotype-based HCM genotype predictor score. Patients clinically diagnosed with HCM and evaluated by genetic counselors comprised the study cohort. Genotype score was derived based on clinical and echocardiographic variables. Total score was correlated with the yield of genetic testing. Of 564 HCM patients, 198 sought genetic testing (35 %; 55 % male; mean age at diagnosis, 50 ± 20 years). Of these, 101 patients (51 %) were genotype positive for a HCM-associated genetic mutation (55 % male; mean age at diagnosis, 42 ± 18 years). Cochran-Armitage analysis showed similar, statistically significant trends of increased yields for higher genotype scores for both the original and study cohort. Validated by the current study, this scoring system provides an easy-to-use, clinical tool to aid in determining the likelihood of a positive HCM genetic test.

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Authors and Affiliations

  1. Mayo Medical School, Mayo Clinic, Rochester, MN, USA

    Sinead L. Murphy & Jamie D. Kapplinger

  2. Department of Pediatric and Adolescent Medicine/Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN, USA

    Jason H. Anderson, Michael J. Ackerman & J. Martijn Bos

  3. Department of Molecular Pharmacology and Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN, USA

    Jamie D. Kapplinger, Michael J. Ackerman & J. Martijn Bos

  4. Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA

    Teresa M. Kruisselbrink

  5. Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA

    Bernard J. Gersh, Steve R. Ommen, Michael J. Ackerman & J. Martijn Bos

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  1. Sinead L. Murphy
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Correspondence to J. Martijn Bos.

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The authors declare that they have no competing interests.

Human Subjects/Informed Consent Statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all the patients for being included in the study. No animal studies were carried out by the authors for this article.

Sources of Funding

This work was supported by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program (MJA). This project was supported by Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Health (NIH).

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Associate Editor Daniel P. Judge oversaw the review of this article

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Yield of genetic testing in each scored subgroup in validation cohort (top) and validation cohort with reclassified variants as likely benign no counted as genotype positive (bottom) (TIF 2028 kb)

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Murphy, S.L., Anderson, J.H., Kapplinger, J.D. et al. Evaluation of the Mayo Clinic Phenotype-Based Genotype Predictor Score in Patients with Clinically Diagnosed Hypertrophic Cardiomyopathy. J. of Cardiovasc. Trans. Res. 9, 153–161 (2016). https://doi.org/10.1007/s12265-016-9681-5

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