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Novel frameshift mutation in Troponin C (TNNC1) associated with hypertrophic cardiomyopathy and sudden death

Published online by Cambridge University Press:  25 January 2011

Wendy K. Chung ,
Carrie Kitner  and
Barry J. Maron
Wendy K. Chung*
Affiliation:
Departments of Pediatrics and Medicine, Columbia University Medical Center, New York
Carrie Kitner
Affiliation:
Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, United States of America
Barry J. Maron
Affiliation:
Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, United States of America
*
Correspondence to: Dr W. Chung, MD PhD, Departments of Pediatrics and Medicine, Columbia University Medical Center, 1150 Street Nicholas Avenue, Room 620, New York 10032, United States of America. Tel: (212)851 5313; Fax: (212)851 5306; E-mail: [email protected]
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Abstract

Purpose

Hypertrophic cardiomyopathy is the most common cause of sudden death in young people, including trained athletes, and is caused by mutations in genes encoding proteins of the cardiac sarcomere. Mutations in the Troponin C gene (TNNC1) are a rare genetic cause of hypertrophic cardiomyopathy. We describe a novel type of mutation (c.363dupG) in Troponin C, a rare form of hypertrophic cardiomyopathy.

Methods

A family in which a 19-year-old asymptomatic male died of sudden cardiac death due to hypertrophic cardiomyopathy was genetically studied by sequencing 17 genes associated with hypertrophic cardiomyopathy or its phenocopies.

Results

A c.363dupG mutation in Troponin C was identified, and tested across the family.

Conclusions

We report the first frameshift mutation (c.363dupG or p.Gln122AlafsX30) in Troponin C causing hypertrophic cardiomyopathy (and sudden cardiac death) in a 19-year-old male, and have demonstrated that the mutation segregates with hypertrophic cardiomyopathy within the family.

Keywords

Geneticsarcomeredominant
Type
Brief Reports
Information
Cardiology in the Young , Volume 21 , Issue 3 , June 2011 , pp. 345 - 348
Copyright
Copyright © Cambridge University Press 2011

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References

1. Maron, BJ, Gardin, JM, Flack, JM, Gidding, SS, Kurosaki, TT, Bild, DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary artery risk development in (young) adults. Circulation 1995; 92: 785–789.Google Scholar
2. Maron, BJ, Doerer, JJ, Haas, TS, Tierney, DM, Mueller, FO. Sudden deaths in young competitive athletes: analysis of 1866 deaths in the U.S., 1980–2006. Circulation 2009; 119: 1085–1092.CrossRefGoogle ScholarPubMed
3. Hoffmann, B, Schmidt-Traub, H, Perrot, A, Osterziel, KJ, Gessner, R. First mutation in cardiac troponin C, L29Q, in a patient with hypertrophic cardiomyopathy. Hum Mutat 2001; 17: 524.Google Scholar
4. Landstrom, AP, Parvatiyar, MS, Pinto, JR, et al. Molecular and functional characterization of novel hypertrophic cardiomyopathy susceptibility mutations in TNNC1-encoded troponin C. J Mol Cell Cardiol 2008; 45: 281–288.CrossRefGoogle ScholarPubMed
5. Mogensen, J, Murphy, RT, Shaw, T, et al. Severe disease expression of cardiac troponin C and T mutations in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 2004; 44: 2033–2040.CrossRefGoogle Scholar
6. Maron, BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA 2002; 287: 1308–1320.Google Scholar
7. Maron, BJ, McKenna, WJ, Danielson, GK, et al. American College of Cardiology/European Society of Cardiology clinical expert consensus document on hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol 2003; 42: 1687–1713.CrossRefGoogle Scholar
8. Lindhout, DA, Sykes, BD. Structure and dynamics of the C-domain of human cardiac troponin C in complex with the inhibitory region of human cardiac troponin I. J Biol Chem 2003; 278: 27024–27034.Google Scholar
9. Maron, BJ, Spirito, P, Shen, WK, et al. Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA 2007; 298: 405–412.CrossRefGoogle ScholarPubMed