Identification of a novel titin-cap/telethonin mutation in a Portuguese family with hypertrophic cardiomyopathy.
Rev Port Cardiol (Engl Ed)
; 39(6): 317-327, 2020 Jun.
Article
em En, Pt
| MEDLINE
| ID: mdl-32565061
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Hipertrófica
/
Proteínas de Transporte
/
Conectina
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
País/Região como assunto:
Europa
Idioma:
En
/
Pt
Ano de publicação:
2020
Tipo de documento:
Article