Unveiling the Spectrum of Minor Genes in Cardiomyopathies: A Narrative Review

Caterina Micolonghi; Federica Perrone; Marco Fabiani; Silvia Caroselli; Camilla Savio; Antonio Pizzuti; Aldo Germani; Vincenzo Visco; Simona Petrucci; Speranza Rubattu; Maria Piane

doi:10.3390/ijms25189787

Unveiling the Spectrum of Minor Genes in Cardiomyopathies: A Narrative Review

Int J Mol Sci. 2024 Sep 10;25(18):9787. doi: 10.3390/ijms25189787.

Authors

Caterina Micolonghi¹, Federica Perrone^{1

2}, Marco Fabiani^{1

3}, Silvia Caroselli^{1

4}, Camilla Savio⁵, Antonio Pizzuti^{1

6}, Aldo Germani⁷, Vincenzo Visco^{5

7}, Simona Petrucci^{5

6

7}, Speranza Rubattu^{5

7

8}, Maria Piane^{5

7}

Affiliations

¹ Department of Experimental Medicine, Faculty of Medicine and Dentistry, Sapienza University of Rome, 00161 Rome, Italy.
² Department of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy.
³ ALTAMEDICA, Human Genetics, 00198 Rome, Italy.
⁴ Juno Genetics, Reproductive Genetics, 00188 Rome, Italy.
⁵ S. Andrea University Hospital, 00189 Rome, Italy.
⁶ Medical Genetics Unit, IRCCS Mendel Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.
⁷ Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy.
⁸ IRCCS Neuromed, 86077 Pozzilli, Italy.

Abstract

Hereditary cardiomyopathies (CMPs), including arrhythmogenic cardiomyopathy (ACM), dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM), represent a group of heart disorders that significantly contribute to cardiovascular morbidity and mortality and are often driven by genetic factors. Recent advances in next-generation sequencing (NGS) technology have enabled the identification of rare variants in both well-established and minor genes associated with CMPs. Nowadays, a set of core genes is included in diagnostic panels for ACM, DCM, and HCM. On the other hand, despite their lesser-known status, variants in the minor genes may contribute to disease mechanisms and influence prognosis. This review evaluates the current evidence supporting the involvement of the minor genes in CMPs, considering their potential pathogenicity and clinical significance. A comprehensive analysis of databases, such as ClinGen, ClinVar, and GeneReviews, along with recent literature and diagnostic guidelines provides a thorough overview of the genetic landscape of minor genes in CMPs and offers guidance in clinical practice, evaluating each case individually based on the clinical referral, and insights for future research. Given the increasing knowledge on these less understood genetic factors, future studies are essential to clearly assess their roles, ultimately leading to improved diagnostic precision and therapeutic strategies in hereditary CMPs.

Keywords: ACM; ARVC; DCM; HCM; cardiomyopathies; genetics.

Publication types

Review

MeSH terms

Cardiomyopathies* / diagnosis
Cardiomyopathies* / genetics
Cardiomyopathy, Dilated / diagnosis
Cardiomyopathy, Dilated / genetics
Cardiomyopathy, Hypertrophic / diagnosis
Cardiomyopathy, Hypertrophic / genetics
Genetic Predisposition to Disease*
High-Throughput Nucleotide Sequencing / methods
Humans
Mutation

Grants and funding

This work was partially funded by Progetto PRIN 2022 (from the Italian Ministry of Instruction, University and Research, no. 2022E75TWB) to S.R. The research leading to these results has also received funding from the European Union-NextGenerationEU through the Italian Ministry of University and Research under PNRR–M4C2-I1.3 Project PE_00000019 “HEAL ITALIA” to S.R., CUP B53C22004000006. The views and opinions expressed are those of the authors only and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the European Commission can be held responsible for them.