Năstasie OC, Radu DA, Onciul S, Drăgoescu MB, Popa-Fotea NM. Nexilin mutations, a cause of chronic heart failure: A state-of-the-art review starting from a clinical case. World J Cardiol 2025; 17(3): 100290 [DOI: 10.4330/wjc.v17.i3.100290]
Corresponding Author of This Article
Nicoleta-Monica Popa-Fotea, MD, PhD, Department of Cardiology, Clinical Emergency Hospital, 8 Floreasca Street, Bucharest 014461, Romania. fotea.nicoleta@yahoo.com
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Cardiol. Mar 26, 2025; 17(3): 100290 Published online Mar 26, 2025. doi: 10.4330/wjc.v17.i3.100290
Nexilin mutations, a cause of chronic heart failure: A state-of-the-art review starting from a clinical case
Oana-Cornelia Năstasie, Dan-Andrei Radu, Sebastian Onciul, Marian-Bogdan Drăgoescu, Nicoleta-Monica Popa-Fotea
Oana-Cornelia Năstasie, Sebastian Onciul, Marian-Bogdan Drăgoescu, Nicoleta-Monica Popa-Fotea, Department of Cardiology, Clinical Emergency Hospital, Bucharest 014461, Romania
Dan-Andrei Radu, Laboratory of Interventional Cardiology, Carol Davila Central Military University Emergency Hospital, Bucharest 010825, Romania
Dan-Andrei Radu, Sebastian Onciul, Nicoleta-Monica Popa-Fotea, Cardio-Thoracic Department, University of Medicine and Pharmacy “Carol Davila”, Bucharest 050474, Romania
Co-first authors: Oana-Cornelia Năstasie and Dan-Andrei Radu.
Author contributions: Năstasie OC, Radu DA, Onciul S, Drăgoescu MB, and Popa-Fotea NM collected and analyzed the data; Popa-Fotea NM drafted the article; Năstasie OC, Radu DA, and Popa-Fotea NM conceived and designed the study, revised the manuscript for important intellectual content; Năstasie OC and Radu DA contributed equally as co-first authors; and all authors read and approved the final version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nicoleta-Monica Popa-Fotea, MD, PhD, Department of Cardiology, Clinical Emergency Hospital, 8 Floreasca Street, Bucharest 014461, Romania. fotea.nicoleta@yahoo.com
Received: August 12, 2024 Revised: January 12, 2025 Accepted: February 18, 2025 Published online: March 26, 2025 Processing time: 220 Days and 16.7 Hours
Abstract
Heart failure (HF) is a medical condition associated with high morbidity and mortality, despite ongoing advances in diagnosis and treatment. Among the various causes of HF, cardiomyopathies are particularly significant and must be thoroughly diagnosed and characterized from the outset. In this review, we aim to present a brief overview of cardiomyopathies as a driver of HF, with a specific focus on the genetic causes, particularly nexilin (NEXN) cardiomyopathy, illustrated by a clinical case. The case involves a 63-year-old male who presented with HF symptoms at moderate exertion. Six months prior, he had been asymptomatic, and a routine transthoracic echocardiography had shown a preserved left ventricular ejection fraction (LVEF). However, during the current evaluation, transthoracic echocardiography revealed a dilated left ventricle with a severely reduced LVEF of 30%. Subsequent coronary angiography ruled out ischemic heart disease, while cardiac magnetic resonance imaging indicated a non-inflammatory, non-infiltrative dilated cardiomyopathy with extensive LV fibrosis. Genetic testing identified a heterozygous in-frame deletion variant in the NEXN gene [c.1949_1951del, p.(Gly650del)], classified as likely pathogenic. State-of-the-art HF treatment was initiated, including cardiac resynchronization therapy with defibrillator support. Following treatment, the patient’s symptoms resolved, and LVEF improved to 42%. Interestingly, this patient experienced the onset of symptoms and left ventricular dysfunction within just six months, a much faster progression compared to previously documented cases where the G650del NEXN variant is typically linked to a more gradual development of dilated cardiomyopathy. Current literature offers limited data on patients with NEXN mutations, and the connection between this gene and both dilated and hypertrophic cardiomyopathies remains an area of active research.
Core Tip: Cardiomyopathies are a leading cause of heart failure, a condition marked by high morbidity and mortality despite continuous advancements in diagnosis and treatment. This review provides a succinct overview of cardiomyopathies, with a particular emphasis on their genetic origins - specifically, nexilin cardiomyopathy - highlighted through the case of a patient diagnosed with this condition. Existing research provides scarce information on individuals carrying nexilin mutations, and the relationship between this gene and cardiomyopathies continues to be actively investigated.
