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The first titin (c.59926 + 1G > A) founder mutation associated with dilated cardiomyopathy
Author(s) -
Hoorntje Edgar T.,
van SpaendonckZwarts Karin Y.,
te Rijdt Wouter P.,
Boven Ludolf,
Vink Aryan,
van der Smagt Jasper J.,
Asselbergs Folkert W.,
van Wijngaarden Jan,
Hennekam Eric A.,
Pinto Yigal M.,
Lekanne Deprez Ronald H.,
BargeSchaapveld Daniela Q.C.M.,
Bootsma Marianne,
Regieli Jakub,
Hoedemaekers Yvonne M.,
Jongbloed Jan D.H.,
van den Berg Maarten P.,
van Tintelen J. Peter
Publication year - 2018
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1002/ejhf.1030
Subject(s) - medicine , dilated cardiomyopathy , titin , proband , founder effect , ejection fraction , exome , cardiology , exome sequencing , cardiomyopathy , heart failure , mutation , genetics , gene , haplotype , biology , sarcomere , myocyte , genotype
Truncating variants in the gene encoding titin (TTNtv) are found in 13–25% of dilated cardiomyopathy (DCM) cases.1,2 In DCM patients, TTNtv are associated with early arrhythmic risk, composed of atrial fibrillation (AF), non-sustained and/or sustained ventricular tachycardia.3 TTNtv in the Aband region, or in constitutively expressed exons of TTN, are generally believed to be pathogenic, but assigning pathogenicity can be challenging because TTNtv are also found in control populations.4 Here we describe the TTN c.59926+1G >A splice-site variant located in the Aband (chr2:179456704C>T, build GRCh37; NM_001267550.2 reference sequence) that we have identified in multiple probands with DCM. Written informed consent was obtained from all participants following local medical ethics committee guidelines. Our study and all experiments conformed with the principles of the Declaration of Helsinki.