biostudies-literatureUnknown17(1)El Chehadeh S<h4>Background</h4>Intellectual disability (ID) is the leading cause of patient referral to medical genetic departments in French academic hospitals. Whole genome sequencing (WGS) as a first diagnostic approach is expected to achieve a higher diagnostic yield than the French national reference strategies (RefStrategy) (fragile X expansion testing, chromosomal microarray analysis, and 44 ID genes panel), given its broad and more homogeneous coverage, its ability to identify copy number, structural and intergenic/deep intronic events.<h4>Methods</h4>DEFIDIAG is a national, prospective pilot investigation, carried out in the framework of the French initiative for genomic medicine (Plan France Médecine Génomique 2025), aimed at comparing the diagnostic yield of WGS trio analysis (WGS-trio) (inGenome medicine110https://www.ebi.ac.uk/biostudies/studies/S-EPMC12495801biostudies-literatureGenome sequencing for the diagnosis of intellectual disability as a paradigm for rare diseases in the French healthcare setting: the prospective DEFIDIAG study.PMC12495801Rossi MGhoumid JBriffaut ASReversat JCoubes CJeannette JVincent-Delorme CVanlerberghe CGoetz NProuteau CEspitalier ADeiller CRomana SLacombe DDollfus HPetiot AHairech NRendja KLe Mestre SCuny CBaujat GCurie AConsolino EBlanchet PBhia WLyonnet SAmiel JFaivre LWillems MDe Nadai NStaraci SGonde DChatron NZiegler ABoland AGeorge HPoe CVoisine ABesse CMoukossi-Mouelle COrmieres CLabalme ASchluth-Bolard CMaillard PYRiccardi FDorian VAbdallah KVincent MTuron VHeide SPillay VBernard CMarzin PBronnec NBaudier MPDieux AThevenon JKeren BLaurent MDe Sainte Agathe JMDenomme-Pichon ASTill MWells CMeyer VBerthiot AMercier SFaudet ASafraou HColin EBruel ALMarlin SHaye DHasnaoui OFauconnier-Fatus CGoldenberg ABusa TRiou APutoux ARougeot-Jung CSaugier-Veber PGlazunova OEsperou HMalan VMuller JLesca GGarde AKhalil MAkloul LBonneau DBardel CChambon PNaudion SSeror VMorel GZordan CCourtin TNguyen Morel MAGerasimenko AWyrebski APetit FNambot SVan Gils JNizon MCaumes RRollier POdent SChennen KLecoquierre FBorel MBuratti JAngelini CHumbert-Asensio MLGoutte SConrad SDuffourd YSandron FTharreau MCarre WJean-Marcais NMouthon LCassinari KDieterich KRubeck CLavillaureix AMarey IMallet AAfenjar AEl Amrani-El Idrissi LHeron DIsidor BPeroni LThauvin CNgom NFGaudry JPoirel EColson CFin BDubourg CMoutet MLEdery PBarth MDuquet RFournier CViora-Dupont EGouvenot KGuimier ASanlaville DHaushalter VPasquier LGerard BCharles PVera GBoute OMargot HLeguern EDeiber CBouctot MLe Tanno PMichot CSimon ALevy-Marchal COlaso RPhilip-Sarles NBarcia GBritel MSchaefer EDe Tayrac MLejeune CPons LBeltram SQuelin CScheidecker SCrantelle LJoly-Helas GGauthier MSaidi MSabour NPiton ASoto MRio MGoizet CHalleb YHaquet EDelanne JCerret FTran Mau-Them FMichaud VGuegan CThambo CRdes Portes VCalmels NVitobello ARollat-Farnier PAFrancois TGuyon LDelmas CPhilippe APhilippe CArmand TBonnefont JPPellen ASDeleuze JFHoudayer CTessarech MRobert FBinquet CDEFIDIAG study groupBournez MMonduc SMignot CTriguel INitschke PGuerrot AMNowak FWhalen SFlorentino VFeger CNugues FMarsili LNicolas GJanuel LBurglen LViard CRPinson LDurand BCormier-Daire VBellengier LGenevieve DMonin PLegendre MMasson CLehalle DEl Chehadeh SFradin MGuillemin FAbdallah HHBacq-Daian DBrehin ACColard MSigaudy SfalseGenome sequencing for the diagnosis of intellectual disability as a paradigm for rare diseases in the French healthcare setting: the prospective DEFIDIAG study.<h4>Background</h4>Intellectual disability (ID) is the leading cause of patient referral to medical genetic departments in French academic hospitals. Whole genome sequencing (WGS) as a first diagnostic approach is expected to achieve a higher diagnostic yield than the French national reference strategies (RefStrategy) (fragile X expansion testing, chromosomal microarray analysis, and 44 ID genes panel), given its broad and more homogeneous coverage, its ability to identify copy number, structural and intergenic/deep intronic events.<h4>Methods</h4>DEFIDIAG is a national, prospective pilot investigation, carried out in the framework of the French initiative for genomic medicine (Plan France Médecine Génomique 2025), aimed at comparing the diagnostic yield of WGS trio analysis (WGS-trio) (in2025-01-01T00:00:00Z2025 Oct2026-06-04T04:21:29.143Z2026-05-04T03:14:19.518ZS-EPMC124958014104477810.1186/s13073-025-01527-4