IDENTIFICATION A NOVEL MUTATION OF TROPONIN-T GENE CAUSING MALIGNANT FORM OF HYPERTROPHIC CARDIOMYOPATHY

Objectives: Genetic origin is important in the development of hypertrophic cardiomyopathy (HCM) which is characterized by myocardial hypertrophy and rhythm disorders. The third most common mutated gene leading to HCM is the troponin-T (TNNT2) gene with an incidence of 2%. Our aim was to analyze mutations of the TNNT2 gene in children and young adults.
Patients and methods: DNA was isolated from peripheral blood of 26 patients followed by PCR (TNNT2 gene, exons 8,11,14,15,16). Mutation analysis was performed using dHPLC and positive chromatograms were sequenced.
Results: One mutation was found in the patient cohort (3,8%). It is a novel mutation, a deletion of a glutamic acid in exon 11, at one of the amino acid positions between 165-168. This mutation has not been published in the literature so far. The patient is a 19 year-old girl, who had endured aborted sudden cardiac death (SCD) twice, so implantation of an implantable cardioverter defibrillator was necessary. Family screening revealed that the patient’s mother also had HCM. Her disease was characterised by mild septal hypertrophy, pronounced fibrosis and an uncommon restrictive diastolic dysfunction. She had suffered malignant arrhythmias several times and died of progressive heart failure at the age of 30. In another patient, two polymorphisms were found in intron 14 (base 18497C>G, base 18585C>T).
Conclusion: We have identified a novel TNNT2 gene mutation which resulted in malignant ventricular arrhythmias and aborted SCD despite a mild myocardial hypertrophy. The phenotype was consistent with the previous data of TNNT2 gene mutations causing HCM published in the literature earlier.