Cardiology in the Young

Brief Reports

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

Wendy K. Chunga1 c1, Carrie Kitnera2 and Barry J. Marona2

a1 Departments of Pediatrics and Medicine, Columbia University Medical Center, New York

a2 Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, United States of America

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.

(Received July 05 2010)

(Accepted October 31 2010)

(Online publication January 25 2011)

Correspondence:

c1 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: wkc15@columbia.edu