{Reference Type}: Case Reports
{Title}: A mutation in the Z-line Cypher/ZASP protein is associated with arrhythmogenic right ventricular cardiomyopathy.
{Author}: Lopez-Ayala JM;Ortiz-Genga M;Gomez-Milanes I;Lopez-Cuenca D;Ruiz-Espejo F;Sanchez-Munoz JJ;Oliva-Sandoval MJ;Monserrat L;Gimeno JR;
{Journal}: Clin Genet
{Volume}: 88
{Issue}: 2
{Year}: Aug 2015
{Factor}: 4.296
{DOI}: 10.1111/cge.12458
{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.