Journal Article Ahead of print
PubMed: 42290130 DOI: 10.1111/cge.70196
Clinical Variability Including Non-Dilated Left Ventricular and Dilated Cardiomyopathy in a Pedigree With an Intragenic CTNNA3 Copy Number Variation.
Clin Genet
Authors: Carmela Fusco, Sandra Mastroianno, Silvia Morlino, Riccardo Pracella, Federica Russo, Ester Maria Lucia Bevere, Orazio Palumbo, Giuseppe Di Stolfo, Marco Castori
Affiliations
- Inborn Errors of Morphogenesis Research Unit and Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy.
- Division of Electrophysiology, Fondazione IRCCS-Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy.
Abstract
CTNNA3 encodes αT-catenin, which contributes to the integrity of the myocardium. Single nucleotide variants are occasionally associated with arrhythmogenic right ventricular cardiomyopathy, and structural variations are apparently enriched in neurodevelopmental disorders. We report a multiplex family in which a ~60 kb microdeletion of CTNNA3 co-segregates with a variable, heart-restricted phenotype including non-dilated left ventricle cardiomyopathy (NDLVC) in one individual and dilated cardiomyopathy in two, with or without apex hypertrabeculation. The intragenic deletion was identified by XONarray and, subsequently, characterized by long-read sequencing after nonconclusive multigene panel testing. This deletion selectively involved exon 9 and was predicted in-frame by removing 153 amino acids and, thus, disrupting the α-catenin/vinculin-like domain, which is critical for proper conformational homodimerization of the encoded αT-catenin. This intragenic deletion co-segregating with NDLVC and dilated cardiomyopathy confirms that CTNNA3 is a candidate gene for hereditary cardiomyopathies.
MeSH
Cardiomyopathy, Dilated, Genes, Catenins, Pedigree, Genetics, Medical, Cardiomyopathies