Late onset sporadic dilated cardiomyopathy caused by a cardiac troponin T mutation

Ana Morales, Jose Renato Pinto, Jill D. Siegfried, Duanxiang Li, Nadine Norton, Mark Hofmeyer, Marta Vallin, Azorides R Morales, James D. Potter, Ray E. Hershberger

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Mutations in TNNT2, encoding cardiac troponin T, commonly shows early onset, aggressive dilated cardiomyopathy (DCM). This observation may influence the decision of whether to undertake clinical genetic testing for TNNT2 in later onset DCM. Further, the trigger for late onset DCM remains enigmatic. A 70-year-old woman, previously healthy with a left ventricular ejection fraction of 50%-55% at age 69, presented with DCM of unknown cause and a 4-month history progressive heart failure requiring cardiac transplantation. Clinical genetic testing revealed a novel TNNT2 R139H mutation but no relevant variants in 18 other DCM genes. Her explanted heart showed partial fatty replacement in the right ventricle. Sequencing for five arrhythmogenic right ventricular dysplasia genes was negative. Functional studies in porcine cardiac skinned fibers reconstituted with the mutant R139H troponin T protein showed decreased Ca2+ sensitivity at pH 7, characteristic of DCM. Because fatty infiltration may acidify the myocellular environment, maximal force development examined at pH 6.5 was diminished, suggesting a possible environmental trigger. We conclude that the TNNT2 R139H mutation was likely to be disease causing. Further, later age of onset may not be relevant to exclude genetic testing for TNNT2 mutations.

Original languageEnglish
Pages (from-to)219-226
Number of pages8
JournalClinical and Translational Science
Volume3
Issue number5
DOIs
StatePublished - Oct 1 2010

Fingerprint

Troponin T
Dilated Cardiomyopathy
Mutation
Genetic Testing
Testing
Genes
Infiltration
Arrhythmogenic Right Ventricular Dysplasia
Fibers
Heart Transplantation
Age of Onset
Stroke Volume
Heart Ventricles
Proteins
Swine
Heart Failure
History

Keywords

  • Dilated cardiomyopathy
  • Genetics

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Morales, A., Pinto, J. R., Siegfried, J. D., Li, D., Norton, N., Hofmeyer, M., ... Hershberger, R. E. (2010). Late onset sporadic dilated cardiomyopathy caused by a cardiac troponin T mutation. Clinical and Translational Science, 3(5), 219-226. https://doi.org/10.1111/j.1752-8062.2010.00228.x

Late onset sporadic dilated cardiomyopathy caused by a cardiac troponin T mutation. / Morales, Ana; Pinto, Jose Renato; Siegfried, Jill D.; Li, Duanxiang; Norton, Nadine; Hofmeyer, Mark; Vallin, Marta; Morales, Azorides R; Potter, James D.; Hershberger, Ray E.

In: Clinical and Translational Science, Vol. 3, No. 5, 01.10.2010, p. 219-226.

Research output: Contribution to journalArticle

Morales, A, Pinto, JR, Siegfried, JD, Li, D, Norton, N, Hofmeyer, M, Vallin, M, Morales, AR, Potter, JD & Hershberger, RE 2010, 'Late onset sporadic dilated cardiomyopathy caused by a cardiac troponin T mutation', Clinical and Translational Science, vol. 3, no. 5, pp. 219-226. https://doi.org/10.1111/j.1752-8062.2010.00228.x
Morales, Ana ; Pinto, Jose Renato ; Siegfried, Jill D. ; Li, Duanxiang ; Norton, Nadine ; Hofmeyer, Mark ; Vallin, Marta ; Morales, Azorides R ; Potter, James D. ; Hershberger, Ray E. / Late onset sporadic dilated cardiomyopathy caused by a cardiac troponin T mutation. In: Clinical and Translational Science. 2010 ; Vol. 3, No. 5. pp. 219-226.
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