biostudies-literaturePagnamenta ATNational Institute for Health Research (NIHR)Wellcome Trust669-679https://www.ebi.ac.uk/biostudies/studies/S-EPMC5477361biostudies-literatureUnknown25(6)Over 150 different proteins attach to the plasma membrane using glycosylphosphatidylinositol (GPI) anchors. Mutations in 18 genes that encode components of GPI-anchor biogenesis result in a phenotypic spectrum that includes learning disability, epilepsy, microcephaly, congenital malformations and mild dysmorphic features. To determine the incidence of GPI-anchor defects, we analysed the exome data from 4293 parent-child trios recruited to the Deciphering Developmental Disorders (DDD) study. All probands recruited had a neurodevelopmental disorder. We searched for variants in 31 genes linked to GPI-anchor biogenesis and detected rare biallelic variants in PGAP3, PIGN, PIGT (n=2), PIGO and PIGL, providing a likely diagnosis for six families. In five families, the variants were in a compound European journal of human genetics : EJHGAnalysis of exome data for 4293 trios suggests GPI-anchor biogenesis defects are a rare cause of developmental disorders.PMC5477361090532/Z/09/ZWT098051Murakami YTaylor JCMansour STemple IKPagnamenta ATDDD StudyFirth RMiller VTadros SPopitsch NHarrison REAnzilotti CJohnson DSTaylor JMHoward MFKini URosser EKinoshita TKerr BfalseAnalysis of exome data for 4293 trios suggests GPI-anchor biogenesis defects are a rare cause of developmental disorders.Over 150 different proteins attach to the plasma membrane using glycosylphosphatidylinositol (GPI) anchors. Mutations in 18 genes that encode components of GPI-anchor biogenesis result in a phenotypic spectrum that includes learning disability, epilepsy, microcephaly, congenital malformations and mild dysmorphic features. To determine the incidence of GPI-anchor defects, we analysed the exome data from 4293 parent-child trios recruited to the Deciphering Developmental Disorders (DDD) study. All probands recruited had a neurodevelopmental disorder. We searched for variants in 31 genes linked to GPI-anchor biogenesis and detected rare biallelic variants in PGAP3, PIGN, PIGT (n=2), PIGO and PIGL, providing a likely diagnosis for six families. In five families, the variants were in a compound 2017-01-01T00:00:00Z2017 Jun2026-05-04T16:22:23.99Z2019-03-27T02:48:01ZS-EPMC54773612832757510.1038/ejhg.2017.32