Author + information
- Received August 8, 1996
- Revision received October 31, 1996
- Accepted November 12, 1996
- Published online March 1, 1997.
- Johanna C Moolman, MSA,
- Valerie A Corfield, PhDA,* (, )
- Berthold Posen, MDB,
- Kholiswa Ngumbela, BSc(Hons)A,
- Christine Seidman, MDC,
- Paul A Brink, MDB and
- Hugh Watkins, MD, PhDCD
- ↵*Dr. Valerie A. Corfield, University of Stellenbosch/Medical Research Council Centre for Molecular and Cellular Biology, P.O. Box 19063, Tygerberg 7505, Republic of South Africa.
Objectives. This study was designed to verify initial observations of the clinical and prognostic features of hypertrophic cardiomyopathy caused by cardiac troponin 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 counseling.
(J Am Coll Cardiol 1997;29:549–55)
☆ Financial support for this study was received from The University of Stellenbosch, Stellenbosch; The South African Medical Research Council, Tygerberg; The Harry and Doris Crossley Fund, Stellenbosch; and the British Heart Foundation, London, England, United Kingdom.
- Received August 8, 1996.
- Revision received October 31, 1996.
- Accepted November 12, 1996.
- The American College of Cardiology
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