Clinical predictors of genetic testing outcomes in hypertrophic cardiomyopathy : Genetics in Medicine : Nature Publishing Group

Clinical predictors of genetic testing outcomes in hypertrophic cardiomyopathy : Genetics in Medicine : Nature Publishing Group

Clinical predictors of genetic testing outcomes in hypertrophic cardiomyopathy

• Jodie Ingles BBiomedSci, PhD,^{ff1, ff2}


• Tanya Sarina MACommsMgmt,^ff1


• Laura Yeates BSc,^ff1


• Lauren Hunt BSc, MSc,^ff3


• Ivan Macciocca BSc, MSc,^{ff4, ff5}


• Louise McCormack MBBS,^ff6


• Ingrid Winship MBChB, MD,^ff5


• Julie McGaughran MBChB, MD,^{ff3, ff7}


• John Atherton MBBS, PhD^{ff6, ff7}


• & Christopher Semsarian MBBS, PhD^{ff1, ff2, ff8}

• Affiliations


• Corresponding author

Journal name:

Genetics in Medicine

(2013)

DOI:

doi:10.1038/gim.2013.44

Received

29 January 2013

Accepted

01 March 2013

Published online

18 April 2013

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Abstract

• Abstract•


• Author information•


• Supplementary information

Purpose:

Genetic testing for hypertrophic cardiomyopathy has been commercially available for almost a decade; however, low mutation detection rate and cost have hindered uptake. This study sought to identify clinical variables that can predict probands with hypertrophic cardiomyopathy in whom a pathogenic mutation will be identified.

Methods:

Probands attending specialized cardiac genetic clinics across Australia over a 10-year period (2002–2011), who met clinical diagnostic criteria for hypertrophic cardiomyopathy and who underwent genetic testing for hypertrophic cardiomyopathy were included. Clinical, family history, and genotype information were collected.

Results:

A total of 265 unrelated individuals with hypertrophic cardiomyopathy were included, with 138 (52%) having at least one mutation identified. The mutation detection rate was significantly higher in the probands with hypertrophic cardiomyopathy with an established family history of disease (72 vs. 29%, P < 0.0001), and a positive family history of sudden cardiac death further increased the detection rate (89 vs. 59%, P < 0.0001). Multivariate analysis identified female gender, increased left-ventricular wall thickness, family history of hypertrophic cardiomyopathy, and family history of sudden cardiac death as being associated with greatest chance of identifying a gene mutation. Multiple mutation carriers (n = 16, 6%) were more likely to have suffered an out-of-hospital cardiac arrest or sudden cardiac death (31 vs. 7%, P = 0.012).

Conclusion:

Family history is a key clinical predictor of a positive genetic diagnosis and has direct clinical relevance, particularly in the pretest genetic counseling setting.

Genet Med advance online publication 18 April 2013

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