Novel frameshift mutation in Troponin C ( TNNC1) associated with hypertrophic cardiomyopathy and sudden death.
PurposeHypertrophic 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.
Departments of Pediatrics and Medicine, Columbia University Medical Center, 1150 St Nicholas Avenue, New York 10032, USA. wkc15@columbia.edu
Wendy K
WK
Chung
Carrie
C
Kitner
Barry J
BJ
Maron
D000293:Adolescent; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D016757:Death, Sudden, Cardiac; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D019209:Troponin C / Q000235:genetics*; D055815:Young Adult
D019209:Troponin C