biostudies-literaturePaine INational Institute of Neurological Disorders and StrokeTelethon FoundationNational Institute of Diabetes and Digestive and Kidney DiseasesCommon Fund of the Office of the Director of the National Institutes of HealthNational Heart, Lung, and Blood InstituteNHGRINational Institutes of HealthNational Human Genome Research InstituteNINDSNHLBITelethonNIDDK NIH HHSWerner Otto Stiftung and the German Research FoundationNHGRI NIH HHSNational Cancer InstituteNINDS NIH HHSNational Institute of Mental HealthNational Institute on Drug AbuseNIGMS NIH HHS302-316https://www.ebi.ac.uk/biostudies/studies/S-EPMC6698803biostudies-literatureUnknown105(2)Members of a paralogous gene family in which variation in one gene is known to cause disease are eight times more likely to also be associated with human disease. Recent studies have elucidated DHX30 and DDX3X as genes for which pathogenic variant alleles are involved in neurodevelopmental disorders. We hypothesized that variants in paralogous genes encoding members of the DExD/H-box RNA helicase superfamily might also underlie developmental delay and/or intellectual disability (DD and/or ID) disease phenotypes. Here we describe 15 unrelated individuals who have DD and/or ID, central nervous system (CNS) dysfunction, vertebral anomalies, and dysmorphic features and were found to have probably damaging variants in DExD/H-box RNA helicase genes. In addition, these individuals exhibit a varieAmerican journal of human geneticsParalog Studies Augment Gene Discovery: DDX and DHX Genes.PMC6698803R01 DK078121U54 HG003273U54-HG003273R01 NS058529T32 NS043124UM1 HG006493K08 HG008986GSP15001T32 GM008307K12 DK083014DK088767UM1 HG006542R35 NS1050782T32NS043124-16TGM16S01R01 DK088767DFG; LE 4223/1Casella EBHildebrandt FRobison RGibbs RAKitajima JPWong BKYWang KOrtega LHempel MUniversity of Washington Center for Mendelian Genomics, Baylor-Hopkins Center for Mendelian Genomics, Telethon Undiagnosed Diseases ProgramBozdogan SLyon GJBierhals TBekheirnia MRKok FLupski JRKleyner RMarmorale TWilichowski EGrochowski CMBayram YHui JYoon MAlikasifoglu MCoban Akdemir ZLessel DMagli AGlass IAydin HVan Esch HWortmann SBVan den Veyver IBJhangiani SNPosey JEJohannsen JCappuccio GSanter RAktas DBrautbar ADorschner MMonteiro FMuzny DMBrunetti-Pierri NRosenheck SKaraca EPaine IItyel HPinelli MYeung WLBamshad MSutton VRWhite JJfalseParalog Studies Augment Gene Discovery: DDX and DHX Genes.Members of a paralogous gene family in which variation in one gene is known to cause disease are eight times more likely to also be associated with human disease. Recent studies have elucidated DHX30 and DDX3X as genes for which pathogenic variant alleles are involved in neurodevelopmental disorders. We hypothesized that variants in paralogous genes encoding members of the DExD/H-box RNA helicase superfamily might also underlie developmental delay and/or intellectual disability (DD and/or ID) disease phenotypes. Here we describe 15 unrelated individuals who have DD and/or ID, central nervous system (CNS) dysfunction, vertebral anomalies, and dysmorphic features and were found to have probably damaging variants in DExD/H-box RNA helicase genes. In addition, these individuals exhibit a varie2019-01-01T00:00:00Z2019 Aug2026-05-02T02:00:00.74Z2021-02-20T00:12:54ZS-EPMC66988033125687710.1016/j.ajhg.2019.06.001