Hypertrophic Cardiomyopathy. A Study of the Troponin-T Gene in 127 Spanish Families

The information available on the correlation between genotype and phenotype and the prognostic implications of different troponin-T gene mutations is sparse and, at times, contradictory. We studied the TNNT2 gene in 127 patients with hypertrophic cardiomyopathy and identified three mutations in patients from four families (3.1%): the Phe87Leu mutation, which has not been previously reported, the Arg278Cys mutation (two families) and the Asp271Ile mutation. Seven carriers of the Phe87Leu mutation (aged 29 to 52 years) were found to have mild hypertrophy (i.e., a wall thickness <16 mm). There were 11 deaths associated with the condition (seven sudden deaths), and four of those who died were aged between 14 and 16 years. No sudden deaths occurred in the other three families. In conclusion, troponin-T mutations were responsible for 3% of the hypertrophic cardiomyopathy cases in our study population. The Phe87Leu mutation was associated with only mild hypertrophy but with a high risk of sudden death.

La información sobre las relaciones genotipo-fenotipo y el pronóstico de las diferentes mutaciones en el gen de la troponina T es escasa y en ocasiones contradictoria.Se realizó estudio del gen TNNT2 en 127 pacientes con miocardiopatía hipertrófica (MCH), identificándose 3 mutaciones en 4 familias (3,1%): Phe87Leu, no descrita, Arg 278Cys (2 familias) y Asp271Ile. Se identificaron 7 portadores de Phe87Leu (29 a 52 años) con hipertrofia leve (grosor < 16 mm). Hubo 11 muertes relacionadas con la enfermedad (7 de ellas súbitas), con 4 de los fallecidos entre 14 y 16 años de edad. No hubo muertes súbitas en las otras 3 familias. En conclusión, las mutaciones en el gen de la troponina T son responsables de un 3% de casos de MCH en nuestra población. La mutación Phe-87Leu se asocia a hipertrofia de grado leve y alto riesgo de muerte súbita.