Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.
Holly A F StessmanBo XiongBradley P CoeTianyun WangKendra HoekzemaMichaela FenckovaMalin KvarnungJennifer GerdtsSandy TrinhNele CosemansLaura VivesJanice LinTychele N TurnerGijs SantenClaudia RuivenkampMarjolein KriekArie van HaeringenEmmelien AtenKathryn FriendJan LiebeltChristopher BarnettEric HaanMarie ShawJozef GeczBritt-Marie AnderlidAnn NordgrenAnna LindstrandCharles SchwartzR Frank KooyGeert VandeweyerCeline HelsmoortelCorrado RomanoAntonino AlbertiMirella VinciEmanuela AvolaStefania GiustoEric CourchesneTiziano PramparoKaren PierceSrinivasa NalaboluDavid G AmaralIngrid E SchefferMartin B DelatyckiPaul J LockhartFereydoun HormozdiariBenjamin HarichAnna Castells-NobauKun XiaHilde PeetersMagnus NordenskjöldAnnette SchenckRaphael A BernierEvan E EichlerPublished in: Nature genetics (2017)
Gene-disruptive mutations contribute to the biology of neurodevelopmental disorders (NDDs), but most of the related pathogenic genes are not known. We sequenced 208 candidate genes from >11,730 cases and >2,867 controls. We identified 91 genes, including 38 new NDD genes, with an excess of de novo mutations or private disruptive mutations in 5.7% of cases. Drosophila functional assays revealed a subset with increased involvement in NDDs. We identified 25 genes showing a bias for autism versus intellectual disability and highlighted a network associated with high-functioning autism (full-scale IQ >100). Clinical follow-up for NAA15, KMT5B, and ASH1L highlighted new syndromic and nonsyndromic forms of disease.