A mutation in the Z-line Cypher/ZASP protein is associated with arrhythmogenic right ventricular cardiomyopathy

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 L...

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Bibliographic Details
Published in:Clinical genetics 2015-08, Vol.88 (2), p.172-176
Main Authors: Lopez-Ayala, J. M., Ortiz-Genga, M., Gomez-Milanes, I., Lopez-Cuenca, D., Ruiz-Espejo, F., Sanchez-Munoz, J. J., Oliva-Sandoval, M. J., Monserrat, L., Gimeno, J. R.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adolescent
Adult
Arrhythmias, Cardiac - genetics
arrhythmogenic right ventricular cardiomyopathy
Arrhythmogenic Right Ventricular Dysplasia - diagnosis
Arrhythmogenic Right Ventricular Dysplasia - genetics
Bundle-Branch Block - diagnosis
Bundle-Branch Block - genetics
Cardiac arrhythmia
Cardiomyopathy
Cypher/ZASP
Desmosomes - genetics
Electrocardiography
Family
Female
Genetic Association Studies
Genetic Testing
Genetics
High-Throughput Nucleotide Sequencing
Humans
LDB3
LIM Domain Proteins - genetics
Male
Middle Aged
Mutation
Mutation, Missense - genetics
next generation sequencing
Pedigree
Proteins
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Summary: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.
ISSN:0009-9163
1399-0004
DOI:10.1111/cge.12458