Identificação de uma nova mutação no gene TCAP/Teletonina numa família portuguesa com miocardiopatia hipertrófica

Translated title of the contribution: Identification of a novel titin-cap/telethonin mutation in a Portuguese family with hypertrophic cardiomyopathy

Alexandra Toste, Andreas Perrot, Cemil Özcelik, Nuno Cardim

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Introduction and objectives: Hypertrophic cardiomyopathy (HCM) is a genetically and phenotypically heterogeneous disease; there is still a large proportion of patients with no identified disease-causing mutation. Although the majority of mutations are found in the MYH7 and MYBPC3 genes, mutations in Z-disk-associated proteins have also been linked to HCM. Methods: We assessed a small family with HCM based on family history, physical examination, 12-lead ECG, echocardiogram and magnetic resonance imaging. After exclusion of mutations in eleven HCM disease genes, we performed direct sequencing of the TCAP gene encoding the Z-disk protein titin-cap (also known as telethonin). Results: We present a novel TCAP mutation in a small family affected by HCM. The identified p.C57W mutation showed a very low population frequency, as well as high conservation across species. All of the bioinformatic prediction tools used considered this mutation to be damaging/deleterious. Family members were screened for this new mutation and a co-segregation pattern was detected. Both affected members of this family presented with late-onset HCM, moderate asymmetric left ventricular hypertrophy, atrial fibrillation and heart failure with preserved ejection fraction and low risk of sudden cardiac death. Conclusions: We present evidence supporting the classification of the TCAP p.C57W mutation, encoding the Z-disk protein titin-cap/telethonin as a new likely pathogenic variant of hypertrophic cardiomyopathy, with a specific phenotype in the family under analysis.

Translated title of the contributionIdentification of a novel titin-cap/telethonin mutation in a Portuguese family with hypertrophic cardiomyopathy
Original languagePortuguese
Pages (from-to)317-327
JournalRevista Portuguesa de Cardiologia
Volume39
Issue number6
DOIs
Publication statusPublished - Jun 2020

Keywords

  • Hypertrophic cardiomyopathy
  • Likely pathogenic variant
  • TCAP mutation
  • Telethonin
  • Titin-cap

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