Biallelic and monoallelic variants in PLXNA1 are implicated in a novel neurodevelopmental disorder with variable cerebral and eye anomalies.
Gabriel C DworschakJaya PunethaJeshurun C KalanithyEnrico MingardoHaktan B ErdemZeynep C AkdemirEnder KaracaTadahiro MitaniDana MarafiJawid M FatihShalini N JhangianiJill V HunterTikam Chand DakalBhanupriya DhabhaiOmar DabbaghHessa S AlsaifFowzan S AlkurayaReza MaroofianHenry HouldenStephanie EfthymiouNatalia DominikVincenzo SalpietroTipu SultanShahzad HaiderFarah BibiHolger ThieleJulia HoefeleKorbinian M RiedhammerMatias WagnerIlaria GuellaMichelle DemosBoris KerenJulien BurattiPerrine CharlesCaroline NavaDelphine HéronSolveig HeideElise ValkanasLeigh B WaddellKristi J JonesEmily C OatesSandra T CooperDaniel MacArthurSteffen SyrbeAndreas ZieglerKonrad PlatzerVolkan OkurWendy K ChungSarah A O'SheaRoy AlcalayStanley FahnPaul R MarkRenzo GuerriniAnnalisa VetroBeth HudsonRhonda E SchnurGeorge E HogansonJennifer E BurtonMeriel McEntagartTobias LindenbergÖznur YilmazBenjamin OdermattDavut PehlivanJennifer E PoseyJames R LupskiHeiko ReutterPublished in: Genetics in medicine : official journal of the American College of Medical Genetics (2021)
We propose that different biallelic and monoallelic variants in PLXNA1 result in a novel neurodevelopmental syndrome mainly comprising developmental delay, brain, and eye anomalies. We hypothesize that biallelic variants in the extracellular Plexin-A1 domains lead to impaired dimerization or lack of receptor molecules, whereas monoallelic variants in the intracellular Plexin-A1 domains might impair downstream signaling through a dominant-negative effect.