biostudies-literatureLaquerriere AAlliance ArthrogryposeInstitut National de la Santé et de la Recherche MédicaleAssociation Française contre les MyopathiesPHRCAgence de Biomédecine559-567https://www.ebi.ac.uk/biostudies/studies/S-EPMC9132874biostudies-literatureUnknown59(6)<h4>Background</h4>Arthrogryposis multiplex congenita (AMC) is characterised by congenital joint contractures in two or more body areas. AMC exhibits wide phenotypic and genetic heterogeneity. Our goals were to improve the genetic diagnosis rates of AMC, to evaluate the added value of whole exome sequencing (WES) compared with targeted exome sequencing (TES) and to identify new genes in 315 unrelated undiagnosed AMC families.<h4>Methods</h4>Several genomic approaches were used including genetic mapping of disease loci in multiplex or consanguineous families, TES then WES. Sanger sequencing was performed to identify or validate variants.<h4>Results</h4>We achieved disease gene identification in 52.7% of AMC index patients including nine recently identified genes (<i>CNTNAP1</i>, <i>MAGEL2</Journal of medical geneticsPhenotypic spectrum and genomics of undiagnosed arthrogryposis multiplex congenita.PMC9132874DAJ18912016AOM101812020Mejlachowicz DLambert LMelki JBucourt MSternberg DVivanti ALetard PQuelin CLatour PLandrieu PLaquerriere AAbiusi ELaffargue FGuimiot FVan Maldergem LVerhelst HMarguet FJouk PSLayet VBlesson SGrigorescu RPerrin LVincent-Delorme CBeneteau CPrieur FAmthor HMercier SMegarbane AAmram DFrancannet CBarnerias CGranier MDieterich KViot GBellesme CColin EMartinovic JGoldenberg ARigonnot LSaada JBiancalana VHeron DAttie-Bitach TStoeva RMunnich ALacombe DEymard BGuiochon-Mantel AGitiaux CDesguerre IBieth EBenachi AJacquemont MLPelluard FLyonnet SAmiel JDelahaye-Duriez ATrestard LQuevarec LCapri YBoucher EFaivre LKhung SWhalen SFallet-Bianco CLoeuillet LBouligand JGut IBessieres BDelezoide ALSaint-Frison MHJaber DBessereau JLMaluenda JMartin-Coignard DGrotto SVerloes ACormier-Daire VTopaloglu HToutain AVincent MLegendre MTawk MRanjatoelina-Randrianaivo HPiard JPetit FGonzales MNizon MResta NNolent FSigaudy SfalsePhenotypic spectrum and genomics of undiagnosed arthrogryposis multiplex congenita.<h4>Background</h4>Arthrogryposis multiplex congenita (AMC) is characterised by congenital joint contractures in two or more body areas. AMC exhibits wide phenotypic and genetic heterogeneity. Our goals were to improve the genetic diagnosis rates of AMC, to evaluate the added value of whole exome sequencing (WES) compared with targeted exome sequencing (TES) and to identify new genes in 315 unrelated undiagnosed AMC families.<h4>Methods</h4>Several genomic approaches were used including genetic mapping of disease loci in multiplex or consanguineous families, TES then WES. Sanger sequencing was performed to identify or validate variants.<h4>Results</h4>We achieved disease gene identification in 52.7% of AMC index patients including nine recently identified genes (<i>CNTNAP1</i>, <i>MAGEL2</2022-01-01T00:00:00Z2022 Jun2026-06-10T03:16:51.303Z2025-04-05T20:38:21.186ZS-EPMC91328743382083310.1136/jmedgenet-2020-107595