biostudies-literatureErkut ECancer Research UKAzrieli FoundationMedical Research CouncilUniversität ZürichNational Institute for Health and Care ResearchHeart of England NHS Foundation TrustWellcome TrustCanadian Institutes of Health Research2625-2642https://www.ebi.ac.uk/biostudies/studies/S-EPMC12808965biostudies-literatureUnknown112(11)Syndromic cardiac malformations can result in morbidity, yet their genetic etiology is only understood for a subset of individuals. Genome sequencing efforts in congenital anomaly cohorts may identify disease-associated variants in previously unrecognized genes. Through international matchmaking efforts, we identified eighteen individuals in total with de novo or loss-of-function variants in EIF3A (n = 4) or EIF3B (n = 14). The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioral abnormalities. These genes encode core subunits of the eukaryotic initiation factor 3 (eIF3) complex, which plays a critical role in binding mRNA transcripts to the 40S ribosomal subunit during translation initiation. Both genes American journal of human geneticsA cardiovascular, craniofacial, and neurodevelopmental disorder caused by loss-of-function variants in the eIF3 complex component genes EIF3A and EIF3B.PMC12808965PJT 178155Lees HQuelin CRanza EStuebben MMcDonald LJeeneea RKoboldt DCDingmann BPerrin LPingault VScott ICZanoni PSchwartz MLBChen XKolokotronis KRauch ALevy JKim RHKupper CKopps AMManshaei RLeonard JGosselin RJobling RKLittlejohn RDubourg CSkraban CMayer DDing QRiedijk ASDiderich KEMSousa SBedoukian ECMcLean SDBlanc XEscobar LFGuillen Sacoto MJPattani NRosmaninho-Salgado JMoran OMSchnurer MTSomerville CConlin LKHaag CDAntonarakis SECox HKenia PErkut EReichert SLHerzig LElmslie FfalseA cardiovascular, craniofacial, and neurodevelopmental disorder caused by loss-of-function variants in the eIF3 complex component genes EIF3A and EIF3B.Syndromic cardiac malformations can result in morbidity, yet their genetic etiology is only understood for a subset of individuals. Genome sequencing efforts in congenital anomaly cohorts may identify disease-associated variants in previously unrecognized genes. Through international matchmaking efforts, we identified eighteen individuals in total with de novo or loss-of-function variants in EIF3A (n = 4) or EIF3B (n = 14). The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioral abnormalities. These genes encode core subunits of the eukaryotic initiation factor 3 (eIF3) complex, which plays a critical role in binding mRNA transcripts to the 40S ribosomal subunit during translation initiation. Both genes 2025-01-01T00:00:00Z2025 Nov2026-07-16T06:47:19.411Z2026-07-09T10:42:06.129ZS-EPMC128089654103330610.1016/j.ajhg.2025.09.008