Prevalence of SOD1 and C9orf72 Variants Among French ALS Population: The GENIALS Study

P Corcia; D Erazo; M D M Amador; S Beltran; E Bernard; H Blasco; C Boutoleau-Bretonniere; G Bruneteau; J P Camdessanche; W Camu; J Cassereau; A Choumert; P Codron; P Cintas; E De La Cruz; V Danel; C Desnuelle; N Eyraud; F Esselin; A L Fauret; M Lefilliatre; M C Fleury; S Genestet; A M Grapperon; N Guy; A Jacquin-Piques; K Beauvais; G Lautrette; G Le Masson; S Mathis; A S Piegay; S Pittion-Vouyovitch; P Sauleau; M H Soriani; A Vershueren; K Mouzat; C Guissart; P Couratier; P Vourc'h

doi:10.1111/ene.70302

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Prevalence of SOD1 and C9orf72 Variants Among French ALS Population: The GENIALS Study

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Prevalence of SOD1 and C9orf72 Variants Among French ALS Population: The GENIALS Study

P Corcia, D Erazo, M D M Amador, S Beltran, E Bernard, H Blasco, C Boutoleau-Bretonniere, G Bruneteau, J P Camdessanche, W Camu, …

European journal of neurology, Vol.32(8), pp.e70302-n/a

08/2025

DOI: https://doi.org/10.1111/ene.70302

PMID: 40751342

Résumé

Adult

Age of Onset

Aged

Amyotrophic Lateral Sclerosis - epidemiology

Amyotrophic Lateral Sclerosis - genetics

C9orf72 Protein

Female

France - epidemiology

Genetic Variation

Humans

Male

Middle Aged

Prevalence

Proteins - genetics

Superoxide Dismutase - genetics

Superoxide Dismutase-1 - genetics

Amyotrophic Lateral Sclerosis (ALS) is a fatal motoneuron disease in which genetics plays a central role for both familial and sporadic ALS cases. Systematic genetic analysis for all ALS patients is recommended at the time of diagnosis, leading to an early proposal of specific genetic therapy. Currently, C9orf72 is considered the most frequently mutated gene in ALS. Patients with a SOD1 pathogenic or probably pathogenic variants (ACMG classification) are eligible for SOD1 antisense oligonucleotide therapy. To determine the frequency of SOD1 variants and C9orf72 G4C2 repeats in a French ALS population and to describe genotype-phenotype relationships. One thousand incident ALS patients were enrolled from 22 ALS centers in France and followed up for 12 months. Epidemiological, familial history, neurological data, and genetic status were collected. C9orf72 G4C2 repeats and SOD1 variants were observed in 7.6% and 1.6%, respectively. Fifty percent of SOD1 patients and 51% of C9orf72 patients had sporadic ALS. Fifteen different SOD1 variants were identified within the five exons and one intron. C9orf72 patients had a significantly younger age at onset and a trend toward a faster progression compared to non-expanded C9orf72 patients. Moreover, among the non-SOD1 non-C9orf72 population, patients with at least one C9orf72 copy with two G4C2 repeats had a shorter disease duration. This study confirms SOD1 variants low frequency in the French population and highlights the more rapid disease progression observed in patients carrying C9orf72 expansions. These findings underscore the importance of systematic genetic screening at diagnosis.

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Titre: Prevalence of SOD1 and C9orf72 Variants Among French ALS Population: The GENIALS Study
Créateurs - sans rôle: P Corcia - Alliance on Clinical Trials for ALS-MND (ACT4ALS-NMD) Network, Bron, France
D Erazo - Centre de Reference SLA et Autres Maladies du Motoneurone, CHU Limoges, Limoges, France
M D M Amador - Sorbonne Université, Paris Brain Institute-ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris (APHP), Hôpital de la Pitié Salpêtrière, Paris, France
S Beltran - Euro-NMD European Reference Network, Paris, France
E Bernard - Centre de Référence Maladies Rares CRMR CHU Lyon, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Université de Lyon, Lyon, France
H Blasco - Service de Biochimie et Biologie moléculaire, CHU de Tours, Tours, France
C Boutoleau-Bretonniere - Département de Neurologie, Centre de Ressources et de Compétence, SLA de Nantes, CHU de Nantes, Nantes, France
G Bruneteau - Assistance Publique – Hôpitaux de Paris
J P Camdessanche - Service de Neurologie, Centre de Ressources et de Compétence SLA, CHU de Saint-Etienne, St-Priest-en-Jarez, France
W Camu - Centre de référence SLA et Autres Maladies du Motoneurone, CHU Montpellier, Montpellier, France
J Cassereau - Mitochondrial and Cardiovascular Physiopathology
A Choumert - Centre de Ressources et de Compétence SLA, CHU la Réunion, La Réunion, France
P Codron - Mitochondrial and Cardiovascular Physiopathology
P Cintas - Centre Ressource et Compétence SLA, CHU Toulouse, Toulouse, France
E De La Cruz - Centre de référence SLA et Autres Maladies du Motoneurone, CHU Montpellier, Montpellier, France
V Danel - Centre de Reference SLA et Autres Maladies Rares du Nerf Moteur, CHU Lille, Lille, France
C Desnuelle - Unité de Recherche Clinique Côte d'Azur
N Eyraud - Euro-NMD European Reference Network, Paris, France
F Esselin - Centre de référence SLA et Autres Maladies du Motoneurone, CHU Montpellier, Montpellier, France
A L Fauret - Sorbonne Université, Department of Genetics, APHP, Hopital de la Pitié-Salpêtrière, Paris, France
M Lefilliatre - Centre Hospitalier Universitaire de Caen Normandie
M C Fleury - Centre Ressource et Compétence SLA, CHU Strasbourg, Strasbourg, France
S Genestet - Centre Ressource et Compétence SLA, CHU Brest, Brest, France
A M Grapperon - Centre de Référence Maladies Rares CRMR SLA CHU La Timone, Marseille, APHM, University Hospital, Marseille, France
N Guy - Centre Ressource et Compétence SLA, CHU Clermont-Ferrand, Clermont Ferrand, France
A Jacquin-Piques - Centre de Ressources et de Compétence SLA, Centre Hospitalier Universitaire Dijon-Bourgogne, Dijon, France
K Beauvais - Centre de Ressources et de Compétence SLA, Centre Hospitalier Universitaire Dijon-Bourgogne, Dijon, France
G Lautrette - Centre de Reference SLA et Autres Maladies du Motoneurone, CHU Limoges, Limoges, France
G Le Masson - Centre de Reference SLA et Autres Maladies Rares du Nerf Moteur, CHU Bordeaux, Bordeaux, France
S Mathis - Centre de Reference SLA et Autres Maladies Rares du Nerf Moteur, CHU Bordeaux, Bordeaux, France
A S Piegay - Euro-NMD European Reference Network, Paris, France
S Pittion-Vouyovitch - Centre Hospitalier Universitaire de Rennes
P Sauleau - Laboratory of Biochemistry and Molecular Biology, Nimes University Hospital, INM, University of Montpellier, Montpellier, France
M H Soriani - Unité de Recherche Clinique Côte d'Azur
A Vershueren - Centre de Référence Maladies Rares CRMR SLA CHU La Timone, Marseille, APHM, University Hospital, Marseille, France
K Mouzat - Centre Ressource et Compétence SLA, CHU Nancy, Nancy, France
C Guissart - Centre Ressource et Compétence SLA, CHU Nancy, Nancy, France
P Couratier - Centre de Reference SLA et Autres Maladies du Motoneurone, CHU Limoges, Limoges, France
P Vourc'h - Service de Biochimie et Biologie moléculaire, CHU de Tours, Tours, France
Détails de publication: European journal of neurology, Vol.32(8), pp.e70302-n/a
Note de subvention: Biogen
Identifiants: 99155138509311
Unité académique: Institut des Neurosciences de Montpellier - INM
Langue: English
Type de ressource: Journal article