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Article Dans Une Revue Circulation: Genomic and Precision Medicine Année : 2023

NEXN gene in cardiomyopathies and sudden cardiac deaths: prevalence, phenotypic expression, and prognosis

1 CHU Amiens-Picardie
2 HEMATIM - HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666
3 IHU ICAN - Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière]
4 UFR Pharmacie UPCité - UFR Pharmacie [Santé] - Université Paris Cité
5 CHU Pitié-Salpêtrière [AP-HP]
6 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
7 HCL - Hospices Civils de Lyon
8 Pôle Cardiovasculaire et Métabolique [CHU Toulouse]
9 hpsj - Groupe Hospitalier Paris Saint-Joseph
10 Service de Cardiologie Maladies Vasculaires [CHU Clermont-Ferrand]
11 Service de cardiologie [CHU La Réunion]
12 Service de cardiologie [Clinique Pasteur - Toulouse]
13 RID-AGE - Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167
14 Service Génétique Médicale [CHU Toulouse]
15 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
16 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
17 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
18 Hôpital Louis Pradel [CHU - HCL]
19 CHU Pointe-à-Pitre / Abymes [Guadeloupe]
20 Service de Génétique Médicale [CHU Poitiers]
21 Hôpital Robert Debré
22 CHU de la Martinique [Fort de France]
23 Hôpitaux La Rochelle Ré Aunis [Groupe hospitalier littoral Atlantique]
24 Centre Hospitalier Métropole Savoie [Chambéry]
25 Département de génétique médicale [Hôpital de la Timone - APHM]
26 Centre de Référence des Cardiomyopathies et des Troubles du Rythme Cardiaque Héréditaires ou Rares [Boulogne-Billancourt]
27 Département de cardiologie
28 Centre Hospitalier de Basse-Terre [Guadeloupe]
29 Service de génétique médicale
30 Departement de Cardiologie [Hôpital Saint-Joseph - Marseille]
31 Département de génétique [Robert Debré]
32 Centre Hospitalier Compiègne-Noyon
33 CHCN - Centre Hospitalier Compiègne-Noyon
34 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
35 Centre Hospitalier de l'Ouest Guyanais Franck Joly [Saint-Laurent-du-Maroni, Guyane Française]
36 Service de Cardiologie [Centre hospitalier Annecy-Genevois, Annecy]
37 Service de Rythmologie
Gilles Millat
Gaël Clerici
Alexandre Janin
Beatrice Kugener
François Lesaffre
Hugues Lucron
François Picard
Caroline Rooryck
Philippe Chevalier
Estelle Gandjbakhch

Résumé

BACKGROUND: Few clinical data are available on NEXN mutation carriers, and the gene’s involvement in cardiomyopathies or sudden death has not been fully established. Our objectives were to assess the prevalence of putative pathogenic variants in NEXN and to describe the phenotype and prognosis of patients carrying the variants. METHODS: DNA samples from consecutive patients with cardiomyopathy or sudden cardiac death/sudden infant death syndrome/idiopathic ventricular fibrillation were sequenced with a custom panel of genes. Index cases carrying at least one putative pathogenic variant in the NEXN gene were selected. RESULTS: Of the 9516 index patients sequenced, 31 were carriers of a putative pathogenic variant in NEXN only, including 2 with double variants and 29 with a single variant. Of the 29 unrelated probands with a single variant (16 males; median age at diagnosis, 32.0 [26.0–49.0] years), 21 presented with dilated cardiomyopathy (prevalence, 0.33%), and 3 presented with hypertrophic cardiomyopathy (prevalence, 0.14%). Three patients had idiopathic ventricular fibrillation, and there were 2 cases of sudden infant death syndrome (prevalence, 0.46%). For patients with dilated cardiomyopathy, the median left ventricle ejection fraction was 37.5% (26.25–50.0) at diagnosis and improved with treatment in 13 (61.9%). Over a median follow-up period of 6.0 years, we recorded 3 severe arrhythmic events and 2 severe hemodynamic events. CONCLUSIONS: Putative pathogenic NEXN variants were mainly associated with dilated cardiomyopathy; in these individuals, the prognosis appeared to be relatively good. However, severe and early onset phenotypes were also observed—especially in patients with double NEXN variants. We also detected NEXN variants in patients with hypertrophic cardiomyopathy and sudden infant death syndrome/idiopathic ventricular fibrillation, although a causal link could not be established.
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Dates et versions

hal-04380043 , version 1 (08-01-2024)

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Citer

Alexis Hermida, Flavie Ader, Gilles Millat, Guillaume Jedraszak, Phillipe Maury, et al.. NEXN gene in cardiomyopathies and sudden cardiac deaths: prevalence, phenotypic expression, and prognosis. Circulation: Genomic and Precision Medicine, 2023, ⟨10.1161/CIRCGEN.123.004285⟩. ⟨hal-04380043⟩
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