Perotto, Maria and Paldino, Alessia and Mazzarotto, Francesco and Barbati, Giulia and Stroeks, Sophie L.V.M. and Verdonschot, Job A.J. and Akhtar, Mohammed and Elliott, Perry and Ochoa, Juan Pablo and Garcia-Pavia, Pablo and de Frutos, Fernando and Sepp, Robert and Hategan, Lidia and Prasad, Sanjay and Yazdani, Momina and Morris-Rosendahl, Deborah and Palinkas, Eszter Dalma and Girolami, Francesca and Olivotto, Iacopo and Parikh, Victoria N. and Fatkin, Diane and Lakdawala, Neal and McKenna, William J. and Stolfo, Davide and Gigli, Marta and Brun, Francesca and Collesi, Chiara and Giacca, Mauro and Zacchigna, Serena and Severini, Giovanni Maria and Lenarduzzi, Stefania and Spedicati, Beatrice and Santin, Aurora and Girotto, Giorgia and Gasparini, Paolo and Taylor, Matthew R.G. and Mestroni, Luisa and Merlo, Marco and Sinagra, Gianfranco and Dal Ferro, Matteo (2025) Genetic and Phenotypic Characterization of Nexilin (NEXN)–Related Cardiomyopathy. JACC: Heart Failure, 13 (9). p. 102529. ISSN 22131779
Full text not available from this repository.Abstract
BACKGROUND: Nexilin (NEXN)-related cardiomyopathies (CMPs) are largely unexplored. OBJECTIVES: This study investigated the causative role of NEXN in CMPs, examining its phenotypic expression and prognostic profile. METHODS: Twelve referral centers collected phenotypic/genotypic data of patients with NEXN variants. Variant rarity was determined according to gnomAD allele frequency in CMPs. Burden enrichment tested rare NEXN variants in hypertrophic (HCM) and dilated cardiomyopathy (DCM)/nondilated left ventricular cardiomyopathy (NDLVC) CMPs against gnomAD non-Finnish Europeans (NFE). Outcomes of validated variants were detailed, with prognostic comparisons to Titin (TTN)- and Filamin C (FLNC)-related CMP cohorts. RESULTS: Involving 60 NEXN carriers with rare, protein-altering variants, a significant enrichment of NEXN-truncating variants (tvs) was found in the DCM/NDLVC cohort (0.39% vs 0.09% in gnomAD NFE; P = 0.0001), whereas no association was observed with HCM. Patients with DCM/NDLVC with NEXNtv (n = 17; median age: 45 years [Q1-Q3: 36-55 years], 88% probands, 53% male) showed mild left ventricular dilatation (indexed end-diastolic volume 69 mL [Q1-Q3: 46-87 mL]), mildly reduced left ventricular ejection fraction (44% [Q1-Q3: 31%-53%]), and myocardial fibrosis (64%). NYHA functional class I was common (71%). During a 45-month median follow-up (Q1-Q3: 11-130 months), 53% of patients were implanted with an implantable cardioverter-defibrillator and 25% had malignant ventricular arrhythmias (MVAs). Compared with TTN-CMP, NEXN-CMP exhibited earlier and more frequent MVAs at higher ejection fractions, and no significant differences were found against FLNC-CMP. CONCLUSIONS: NEXNtvs were significantly associated with DCM/NDLVC, characterized by mild cardiac abnormalities, infrequent heart failure, common fibrosis, and arrhythmias. This largest NEXN variant carrier cohort to date contributes to defining the causative role of this rare genotype and its associated phenotype.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 04 Dec 2025 04:18 |
| Last Modified: | 04 Dec 2025 04:18 |
| URI: | http://eprints.victorchang.edu.au/id/eprint/1762 |
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