title: Sudden death due to troponin T mutations.
abstract: OBJECTIVE
  This study was designed to verify initial observations of the clinical and prognostic features of hypertrophic cardiomyopathy caused by cardiac tropnin T gene mutations.
  
  
  BACKGROUND
  The most common cause of sudden cardiac death in the young is hypertrophic cardiomyopathy, which is usually familial. Mutations causing familial hypertrophic cardiomyopathy have been identified in a number of contractile protein genes, raising the possibility of genetic screening for subjects at risk. A previous report suggested that mutations in the cardiac troponin T gene were notable because they were associated with a particularly poor prognosis but only mild hypertrophy. Given the variability of some genotype:phenotype correlations, further analysis of cardiac troponin T mutations has been a priority.
  
  
  METHODS
  Deoxyribonucleic acid from subjects with hypertrophic cardiomyopathy was screened for cardiac troponin T mutations using a ribonuclease protection assay. Polymerase chain reaction-based detection of a novel mutation was used to genotype members of two affected pedigrees. Gene carriers were examined by echocardiography and electrocardiology, and a family history was obtained.
  
  
  RESULTS
  A novel cardiac troponin T gene mutation, arginine 92 tryptophan, was identified in 19 of 48 members of two affected pedigrees. The clinical phenotype was characterized by minimal hypertrophy (mean [+/-SD] maximal ventricular wall thickness 11.3 +/- 5.4 mm) and low disease penetrance by clinical criteria (40% by echocardiography) but a high incidence of sudden cardiac death (mean age 17 +/- 9 years).
  
  
  CONCLUSIONS
  These data support the observation that apparently diverse cardiac troponin T gene mutations produce a consistent disease phenotype. Because this is one of poor prognosis, despite deceptively mild or undetectable hypertrophy, genotyping at this locus may be particularly informative in patient management and counselling.
authors.affiliation: University of Stellenbosch, Tygerberg, Republic of South Africa.
authors.forename: J C
authors.initials: JC
authors.lastname: Moolman
authors.forename: V A
authors.initials: VA
authors.lastname: Corfield
authors.forename: B
authors.initials: B
authors.lastname: Posen
authors.forename: K
authors.initials: K
authors.lastname: Ngumbela
authors.forename: C
authors.initials: C
authors.lastname: Seidman
authors.forename: P A
authors.initials: PA
authors.lastname: Brink
authors.forename: H
authors.initials: H
authors.lastname: Watkins
mesh_terms: D015415:Biomarkers; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000235:genetics* / Q000401:mortality; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D005838:Genotype; D006801:Humans; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011379:Prognosis; D016019:Survival Analysis; D014336:Troponin / Q000235:genetics*; D020107:Troponin T
chemical_list: D015415:Biomarkers; D014336:Troponin; D020107:Troponin T