Genetic Analysis of Patients with Left Ventricular Noncompaction: Identification of Novel Candidate Variants

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Background: Left ventricular noncompaction (LVNC) is a myocardial abnormality char-acterized by prominent trabeculations, a thin compacted layer, and deep intertrabecular recesses. LVNC is a heterogeneous myocardial disorder of uncertain etiology, which may occur as a congenital or acquired condition or develop in association with other cardio-myopathies. Genetic factors have also been implicated in its pathogenesis. Objectives: The aim of this study was to investigate the genetic background of patients with LVNC through next-generation sequencing (NGS) analysis and to identify potentially dis-ease-associated variants. Methods: Twenty-five patients with LVNC underwent genetic testing by NGS using the Ion Torrent™ platform. Variants identified by NGS were con-firmed by Sanger sequencing. The interpretation was performed according to ACMG guidelines using multiple bioinformatic and clinical databases. Results: Genetic variants were identified in 13 patients, with 14 variants detected in 9 genes (TTN, MYH7, CTNNA3, DSG2, FLNC, JPH2, NKX2-6, TNNC1, and JUP). Eight variants (57%) were nov-el, four (29%) had been previously reported in clinical cases without scientific discussion, and two (14%) were already described in the literature. According to ACMG criteria, vari-ants were classified as pathogenic (n=1), likely pathogenic (n=7), or variants of uncertain significance (n=5). Conclusions: These findings highlight the marked genetic heterogenei-ty of LVNC and support the role of genetic testing in improving diagnosis, risk stratifica-tion and clinical management.

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