title: A mutation in the Z-line Cypher/ZASP protein is associated with arrhythmogenic right ventricular cardiomyopathy.
abstract: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of malignant arrhythmia and sudden death particularly in young people. Although it is considered a desmosomal disease, mutations in non-desmosomal genes have also been identified. We report on a family where a mutation in LDB3 is associated with this condition. The index case and first and second degree relatives underwent a complete clinical evaluation: physical examination, electrocardiography (ECG), signal-averaged ECG, 2D echocardiogram, cardiac magnetic resonance and 24-h monitoring. After ruling out mutations in the five desmosomal genes, genetic testing by means of Next Generation Sequencing was carried out on the proband. A heterozygous missense mutation in LDB3 c.1051A>G was identified. This result was confirmed by subsequent Sanger DNA sequencing. Another six carriers were identified amongst her relatives. Three subjects fulfilled the criteria for a definitive diagnosis of ARVC and one reached a borderline diagnosis. In conclusion, this is the first family with ARVC where a mutation in LDB3 is associated with ARVC. Next generation sequencing arises as a particular useful tool to point to new causative genes in ARVC.
authors.affiliation: Department of Cardiology, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Lopez-Ayala
authors.affiliation: A Coruña Biomedical Research Institute, A Coruña University Hospital, A Coruna, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ortiz-Genga
authors.affiliation: Department of Clinical Analysis, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Gomez-Milanes
authors.affiliation: Department of Cardiology, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Lopez-Cuenca
authors.affiliation: Department of Clinical Analysis, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Ruiz-Espejo
authors.affiliation: Department of Cardiology, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Sanchez-Munoz
authors.affiliation: Department of Cardiology, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Oliva-Sandoval
authors.affiliation: A Coruña Biomedical Research Institute, A Coruña University Hospital, A Coruna, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Monserrat
authors.affiliation: Department of Cardiology, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: J R
authors.initials: JR
authors.lastname: Gimeno
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001145:Arrhythmias, Cardiac / Q000235:genetics*; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis / Q000235:genetics*; D002037:Bundle-Branch Block / Q000175:diagnosis / Q000235:genetics; D003896:Desmosomes / Q000235:genetics; D004562:Electrocardiography; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C120696:LDB3 protein, human; D060588:LIM Domain Proteins
keywords: Cypher/ZASP; LDB3; arrhythmogenic right ventricular cardiomyopathy; next generation sequencing