%0 Journal Article
%T Identification of a novel titin-cap/telethonin mutation in a Portuguese family with hypertrophic cardiomyopathy.
%A Toste A
%A Perrot A
%A Özcelik C
%A Cardim N
%J Rev Port Cardiol (Engl Ed)
%V 39
%N 6
%D Jun 2020
%M 32565061
暂无%R 10.1016/j.repc.2019.12.007
%X <B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>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).<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.