Christopher T. GordonShifeng XueGökhan YigitHicham FilaliKelan ChenNadine RosinKoh Ichiro YoshiuraMyriam OufademTamara J. BeckRuth McGowanAlex C. MageeJanine AltmüllerCamille DionHolger ThieleAlexandra D. GurzauPeter NürnbergDieter MeschedeWolfgang MühlbauerNobuhiko OkamotoVinod VargheseRachel IrvingSabine SigaudyDenise WilliamsS. Faisal AhmedCarine BonnardMung Kei KongIlham RatbiNawfal FejjalMeriem FikriSiham Chafai ElalaouiHallvard ReigstadChristine Bole-FeysotPatrick NitschkéNicola RaggeNicolas LévyGökhan TunçbilekAudrey S.M. TeoMichael L. CunninghamAbdelaziz SefianiHülya KayseriliJames M. MurphyChalermpong ChatdokmaipraiAxel M. HillmerDuangrurdee WattanasirichaigoonStanislas LyonnetFrédérique MagdinierAsif JavedMarnie E. BlewittJeanne AmielBernd WollnikBruno ReversadeInsermUniversite Paris DescartesA-Star, Institute of Medical BiologyA-Star, Institute of Molecular and Cell BiologyUniversitätsmedizin GöttingenMohammed V University in RabatWalter and Eliza Hall Institute of Medical ResearchUniversity of MelbourneNagasaki UniversityQueen Elizabeth University HospitalBelfast Health and Social Care TrustUniversity of CologneGenetique Medicale et Genomique FonctionnelleInstitut für HumangenetikFacharzt fur plastische und asthetische ChirurgieResearch Institute, Osaka Medical Center for Maternal and Child HealthUniversity Hospital of WalesHopital La TimoneNHS Foundation TrustUniversity of GlasgowNational Institute of HygieneHelse Bergen Haukeland University HospitalOxford Brookes UniversityHacettepe ÜniversitesiA-Star, Genome Institute of SingaporeUniversity of Washington School of MedicineKoç ÜniversitesiMahidol UniversityHôpital Necker Enfants MaladesNational University of SingaporeVU University Medical Center2018-12-212019-03-142018-12-212019-03-142017-01-31Nature Genetics. Vol.49, No.2 (2017), 249-25515461718106140362-s2.0-85008686533https://repository.li.mahidol.ac.th/handle/20.500.14594/41957© 2017 Nature America, Inc. All rights reserved. Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/ng.3765