http://www.cnr.it/ontology/cnr/individuo/prodotto/ID276154

\"Doubly heterozygous LMNA and TTN Mutations Revealed by Exome Sequencing in a Severe Form of Dilated Cardiomyopathy\". (Articolo in rivista)

Type

Prodotto della ricerca (Classe)
Articolo in rivista (Classe)

Label

\"Doubly heterozygous LMNA and TTN Mutations Revealed by Exome Sequencing in a Severe Form of Dilated Cardiomyopathy\". (Articolo in rivista) (literal)

Anno

2013-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1038/ejhg.2013.16 (literal)

Alternative label

Roberta Roncarati1,2, Chiara Viviani Anselmi2, Peter Krawitz3,4,5, Giovanna Lattanzi6, Yskert von Kodolitsch7, Andreas Perrot8,9, Elisa di Pasquale2,10, Laura Papa2, Paola Portararo2, Marta Columbaro6, Alberto Forni11, Giuseppe Faggian11, Gianluigi Condorelli1,12 and Peter N Robinson3,4,5 (2013)
"Doubly heterozygous LMNA and TTN Mutations Revealed by Exome Sequencing in a Severe Form of Dilated Cardiomyopathy".
in European journal of human genetics (Online); Editore: Nature Publishing Group -, Baltimore, Md. (Stati Uniti d'America)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Roberta Roncarati1,2, Chiara Viviani Anselmi2, Peter Krawitz3,4,5, Giovanna Lattanzi6, Yskert von Kodolitsch7, Andreas Perrot8,9, Elisa di Pasquale2,10, Laura Papa2, Paola Portararo2, Marta Columbaro6, Alberto Forni11, Giuseppe Faggian11, Gianluigi Condorelli1,12 and Peter N Robinson3,4,5 (literal)

Pagina inizio

1105 (literal)

Pagina fine

1111 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

http://www.nature.com/ejhg/journal/v21/n10/full/ejhg201316a.html (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

21 (literal)

Rivista

European journal of human genetics (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

6 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

1Biomedical and Genetic Research Institute (IRGB), Milan Unit, National Research Council of Italy, Milan, Italy 2Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy 3Institute of Medical Genetics and Human Genetics, Charité Universitätsmedizin, Berlin, Germany 4Berlin-Brandenburg Center for Regenerative Therapies, Charité Universitätsmedizin, Berlin, Germany 5Max Planck Institute for Molecular Genetics, Berlin, Germany 6National Research Council of Italy, Institute of Molecular Genetics, Laboratory of Musculoskeletal Cell Biology, Rizzoli Orthopedic Institute, Bologna, Italy 7Centre of Cardiology and Cardiovascular Surgery, University Hospital Eppendorf, Hamburg, Germany 8Department of Cardiology, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany 9Experimental and Clinical Research Center (ECRC), Charité and the Max Delbrück Center for Molecular Medicine, Berlin, Germany 10Institute of Genetic and Biomedical Research (IRGB), National Research Council (CNR), Milan, Italy 11Division of Cardiac Surgery, University of Verona, Verona, Italy 12Humanitas Clinical and Research Center, Milan, Italy (literal)

Titolo

\"Doubly heterozygous LMNA and TTN Mutations Revealed by Exome Sequencing in a Severe Form of Dilated Cardiomyopathy\". (literal)

Abstract

Familial dilated cardiomyopathy (DCM) is a heterogeneous disease; although 30 disease genes have been discovered, they explain only no more than half of all cases; in addition, the causes of intra-familial variability in DCM have remained largely unknown. In this study, we exploited the use of whole-exome sequencing (WES) to investigate the causes of clinical variability in an extended family with 14 affected subjects, four of whom showed particular severe manifestations of cardiomyopathy requiring heart transplantation in early adulthood. This analysis, followed by confirmative conventional sequencing, identified the mutation p.K219T in the lamin A/C gene in all 14 affected patients. An additional variant in the gene for titin, p.L4855F, was identified in the severely affected patients. The age for heart transplantation was substantially less for LMNA:p.K219T/TTN:p.L4855F double heterozygotes than that for LMNA:p.K219T single heterozygotes. Myocardial specimens of doubly heterozygote individuals showed increased nuclear length, sarcomeric disorganization, and myonuclear clustering compared with samples from single heterozygotes. In conclusion, our results show that WES can be used for the identification of causal and modifier variants in families with variable manifestations of DCM. In addition, they not only indicate that LMNA and TTN mutational status may be useful in this family for risk stratification in individuals at risk for DCM but also suggest titin as a modifier for DCM. (literal)

Editore