Cor Vasa 2008, 50(6):242-245 | DOI: 10.33678/cor.2008.080

Our initial experience with genetic testing of patients with hypertrophic cardiomyopathy: mutations of troponin T and troponin I genes

Karol Čurila¹, Martin Pěnička¹, Marek Minárik², Hana Línková¹, Lucie Benešová², Pavel Gregor¹

¹ III. interní-kardiologická klinika, Kardiocentrum, Fakultní nemocnice Královské Vinohrady a 3. lékařská fakulta Univerzity Karlovy

² Laboratoř molekulární genetiky Genomac International, s. r. o., Praha, Česká republika

Introduction:
Hypertrophic cardiomyopathy (HCM) is an autosomal hereditary dominant disorder caused by mutations in genes encoding cardiac sarcomeric proteins. Troponin T and troponin I make an important part of the heart muscle sarcomere and mutations in their genes are responsible for developing HCM. The frequency of these 2 genes is reported to be about 3-15%.

Method:
We studied the prevalence of mutations in troponin T and troponin I genes in 40 individuals with HCM on follow-up in the Heart Center of a Prague-based hospital. DNA samples were genetically tested using direct bidirectional sequencing of PCR products. Genetic testing was performed in exons 8-11 and 14-16 in TNNT2 and exons 5, 7, and 8 in TNNI3.

Results:
The disease causing mutation was found in 3 (7.5%) patients. All mutations were present only in the troponin I gene, in exon 7 (2 x Arg141Gln and 1 x Ala157Val). Further genetic testing identified a total of another 4 mutation carriers in the affected families. The subjects were characterized by mild symptoms and moderate left ventricular hypertrophy (mean maximum septal wall thickness 23 ± 3 mm). An increased incidence od sudden cardiac death, both in young and adult age, was observed in a family with the Ala157Val mutation.

Conclusion:
We observed a higher incidence (7.5%) of troponin I gene mutations and no mutation in the troponin T gene in our group of HCM patients. While patients with mutations were characterized by mild symptoms, an increased risk for sudden death was noted in the family with the Ala157Val mutation.

Keywords: Hypertrophic cardiomyopathy; Genes; Mutations; Troponin I; Troponin T

Published: June 1, 2008  Show citation