| Title: |
Spectrum of Phenotypes in SMA Patients With 4 SMN2 Copies in the French Population |
| Authors: |
Gerin, Lorène; Ropars, Juliette; Garcia-Uzquiano, Rocío; Gómez-García de la Banda, Marta; Saugier-Veber, Pascale; Desguerre, Isabelle; Salort-Campana, Emmanuelle; Espil, Caroline; Barnerias, Christine; Laugel, Vincent; Cances, Claude; Audic, Frederique; Cintas, Pascal; Le Goff, Laure; Mallaret, Martial; Nouguès, Marie-Christine; Drunat, Séverine; Tard, Céline; Grimaldi, Lamiae; Quijano-Roy, Susana |
| Contributors: |
Filière Neuromusculaire (FILNEMUS); Hôpital Raymond Poincaré (Garches) GHU AP-HP Université Paris-Saclay; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Laboratoire de Traitement de l'Information Medicale (LaTIM); Université de Brest (UBO EPE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique); Institut Mines-Télécom Paris (IMT)-Institut Mines-Télécom Paris (IMT)-Institut Brestois Santé Agro Matière (IBSAM); Université de Brest (UBO EPE); Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND); Université de Rouen Normandie (UNIROUEN); Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM); Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Neurologie, maladies neuro-musculaires Hôpital de la Timone - APHM; Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Timone CHU - APHM (TIMONE); CHU de Bordeaux Pellegrin Bordeaux; Pôle de pédiatrie CHU de Strasbourg; Centre Hospitalier Universitaire Strasbourg (CHU Strasbourg); Hôpitaux Universitaires de Strasbourg (HUS)-Hôpitaux Universitaires de Strasbourg (HUS)-Hôpital de Hautepierre Strasbourg; Hôpitaux Universitaires de Strasbourg (HUS); Service Neurologie Pédiatrique CHU Toulouse; Pôle Enfants CHU Toulouse; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse); Hospices Civils de Lyon (HCL); GIN Grenoble Institut des Neurosciences (GIN); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA); Pôle Psychiatrie et Neurologie Grenoble; CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble (CHUGA); CHU Trousseau APHP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Département de génétique Robert Debré; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré Paris; Lille Neurosciences & Cognition - U 1172 (LilNCog); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); AP-HP. Université Paris Saclay; Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP); Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM); Service de réanimation medico-chirurgicale CHU Raymond-Poincaré; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré AP-HP |
| Source: |
EISSN: 2376-7839 ; Neurology Genetics ; https://hal.science/hal-05059776 ; Neurology Genetics, 2025, 11 (2), ⟨10.1212/nxg.0000000000200222⟩ |
| Publisher Information: |
CCSD; American Academy of Neurology |
| Publication Year: |
2025 |
| Collection: |
Université de Versailles Saint-Quentin-en-Yvelines: HAL-UVSQ |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; Clinical phenotype and course of individuals with 4 copies of the SMN2 gene are insufficiently described, and presymptomatic treatment remains controversial. This is a cohort study that analyzed data from SMA patients with zero SMN1 and 4 SMN2 copies collected in the "Registre SMA France" to describe epidemiology, clinical presentation, and course. A total of 140 of 1,112 patients with SMA carried 4 SMN2 copies (16% of those with available SMN2 copy number). The median age at onset was 3.5 years (6 months-20 years), and the median follow-up was 32 years. Twelve patients (8.6%) did not walk independently (SMA2). Of them, most were able to stand or walk with support (72%). Independent walking was acquired in 91% (123 SMA3, 5 SMA4), and one-third of them lost this ability (median 16 years). Loss of ambulation was significantly earlier in children with onset before 3 years (SMA3a). There was a significant predominance of male participants in the whole cohort (63%) and in subcohorts (SMA2, 83%; SMA3, 61%; adult population, 68%). There was a significant lower risk for female participants to lose ambulation (p = 0.01). Sixty-five percent of patients used a wheelchair. Scoliosis surgery and ventilation were required in less than 15%. Most SMA patients with 4 SMN2 copies in the French population show an onset during childhood and a progressive course with absence or loss of ambulation before adulthood. Presymptomatic treatment seems an acceptable option to consider, although identification of individual pejorative markers of early or severe phenotypes would allow more targeted approaches. Our results and literature suggest a gender effect in this population. NCT04177134. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/40212804; PUBMED: 40212804 |
| DOI: |
10.1212/nxg.0000000000200222 |
| Availability: |
https://hal.science/hal-05059776; https://hal.science/hal-05059776v1/document; https://hal.science/hal-05059776v1/file/gerin-et-al-2025-spectrum-of-phenotypes-in-sma-patients-with-4-smn2-copies-in-the-french-population.pdf; https://doi.org/10.1212/nxg.0000000000200222 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.7AEE929F |
| Database: |
BASE |