%0 Journal Article %T Effect of familial clustering in the genetic screening of 235 French ALS families %+ Service de Neurologie, CHU Tours %+ UMR U 1253 %+ Université de Montpellier (UM) %+ Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier) %+ Service de Neurologie [CHU Limoges] %+ Neuroépidémiologie Tropicale (NET) %+ Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E) %+ Département Neurologie [CHU Toulouse] %+ centre de références des maladies neuromusculaires %+ Centre Hospitalier Universitaire de Nice (CHU Nice) %+ Service de Neurologie [CHU Strasbourg] %+ Centre de compétence de la Sclérose Latérale Amyotrophique [CHU Clermont-Ferrand] (SLA) %+ Unité de Neurologie, Département de Neurologie, CHU d’Angers, Angers, France %+ Neuropsychologie et imagerie de la mémoire humaine (NIMH) %+ Centre Hospitalier Universitaire de Nancy (CHU Nancy) %+ Département de Pharmacologie Médicale [Lille] (Pôle Recherche) %+ CHU de Saint-Brieuc %+ Service de neurologie [Bordeaux] %+ Université Francois Rabelais [Tours] %+ CHU Pitié-Salpêtrière [AP-HP] %+ Hopital universitaire de Lyon %+ UMR 1253, iBrain, Imagerie et cerveau (iBrain - Université de Tours, Inserm) %+ Service de Médecine Nucléaire [Tours] %A Corcia, Philippe %A Camu, William %A Brulard, Celine %A Marouillat, Sylviane %A Couratier, Philippe %A Camdessanché, Jean-Philippe %A Cintas, Pascal %A Verschueren, Annie %A Soriani, Marie-Helene %A Desnuelle, Claude %A Fleury, Marie-Céline %A Guy, Nathalie %A Cassereau, Julien %A Viader, Fausto %A Pittion-Vouyovitch, Sophie %A Danel, Veronique %A Kolev, Ivan %A Le Masson, Gwendal %A Beltran, Stephane %A Salachas, Francois %A Bernard, Emilien %A Pradat, Pierre-François %A Blasco, Hélène %A Lanznaster, Débora %A Hergesheimer, Rudolph %A Laumonnier, Frederic %A Andres, Christian %A Meininger, Vincent %A Vourc'H, Patrick %< avec comité de lecture %@ 0022-3050 %J Journal of Neurology, Neurosurgery and Psychiatry %I BMJ Publishing Group %V 92 %N 5 %P 479-484 %8 2021-04-15 %D 2021 %R 10.1136/jnnp-2020-325064 %Z Life Sciences [q-bio]/Santé publique et épidémiologieJournal articles %X Objectives To determine whether the familial clustering of amyotrophic lateral sclerosis (ALS) cases and the phenotype of the disease may help identify the pathogenic genes involved. Methods We conducted a targeted next-generation sequencing analysis on 235 French familial ALS (FALS), unrelated probands to identify mutations in 30 genes linked to the disease. The genealogy, that is, number of cases and generations with ALS, gender, age, site of onset and the duration of the disease were analysed. Results Regarding the number of generations, 49 pedigrees had only one affected generation, 152 had two affected generations and 34 had at least three affected generations. Among the 149 pedigrees (63.4%) for which a deleterious variant was found, an abnormal G4C2 expansion in C9orf72 was found in 98 cases as well as SOD1 , TARBP or FUS mutations in 30, 9 and 7 cases, respectively. Considering pedigrees from the number of generations, abnormal G4C2 expansion in C9orf72 was more frequent in pedigrees with pairs of affected ALS cases, which represented 65.2% of our cohort. SOD1 mutation involved all types of pedigrees. No TARDBP nor FUS mutation was present in monogenerational pedigrees. TARDBP mutation predominated in bigenerational pedigrees with at least three cases and FUS mutation in multigenerational pedigrees with more than seven cases, on average, and with an age of onset younger than 45 years. Conclusion Our results suggest that familial clustering, phenotypes and genotypes are interconnected in FALS, and thus it might be possible to target the genetic screening from the familial architecture and the phenotype of ALS cases. %G English %L hal-03369962 %U https://unilim.hal.science/hal-03369962 %~ INSERM %~ UNILIM %~ EPHE %~ UNIV-TOURS %~ APHP %~ NET %~ SANTE_PUB_INSERM %~ GEIST %~ COMUE-NORMANDIE %~ PSL %~ UNIV-MONTPELLIER %~ UNICAEN %~ SORBONNE-UNIVERSITE %~ SORBONNE-UNIV %~ NIMH %~ SU-MEDECINE %~ TEST-DEV %~ SU-MED %~ CHU-CLERMONTFERRAND %~ EPHE-PSL %~ ALLIANCE-SU %~ EPIMACT %~ OMEGAHEALTH %~ UM-2015-2021 %~ LABCIS