Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
Zhao S, Mekbib K, van der Ent M, Allington G, Prendergast A, Chau J, Smith H, Shohfi J, Ocken J, Duran D, Furey C, Hao L, Duy P, Reeves B, Zhang J, Nelson-Williams C, Chen D, Li B, Nottoli T, Bai S, Rolle M, Zeng X, Dong W, Fu P, Wang Y, Mane S, Piwowarczyk P, Fehnel K, See A, Iskandar B, Aagaard-Kienitz B, Moyer Q, Dennis E, Kiziltug E, Kundishora A, DeSpenza T, Greenberg A, Kidanemariam S, Hale A, Johnston J, Jackson E, Storm P, Lang S, Butler W, Carter B, Chapman P, Stapleton C, Patel A, Rodesch G, Smajda S, Berenstein A, Barak T, Erson-Omay E, Zhao H, Moreno-De-Luca A, Proctor M, Smith E, Orbach D, Alper S, Nicoli S, Boggon T, Lifton R, Gunel M, King P, Jin S, Kahle K. Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations. Nature Communications 2023, 14: 7452. PMID: 37978175, PMCID: PMC10656524, DOI: 10.1038/s41467-023-43062-z.Peer-Reviewed Original ResearchConceptsEphrin receptor B4Galen malformationBrain arteriovenous malformationsP120 RasGAPTransmitted variantsArteriovenous malformationsDe novo variantsSingle-cell transcriptomesSignificant burdenCerebrovascular developmentIntegrative genomic analysisEndothelial cellsVenous networkAdditional probandsMalformationsNovo variantsMissense variantsGenomic analysisDevelopmental angiogenesisVascular developmentDamaging variantsVeinRasGAPIntegrated analysisPatientsMultiomic analyses implicate a neurodevelopmental program in the pathogenesis of cerebral arachnoid cysts
Kundishora A, Allington G, McGee S, Mekbib K, Gainullin V, Timberlake A, Nelson-Williams C, Kiziltug E, Smith H, Ocken J, Shohfi J, Allocco A, Duy P, Elsamadicy A, Dong W, Zhao S, Wang Y, Qureshi H, DiLuna M, Mane S, Tikhonova I, Fu P, Castaldi C, López-Giráldez F, Knight J, Furey C, Carter B, Haider S, Moreno-De-Luca A, Alper S, Gunel M, Millan F, Lifton R, Torene R, Jin S, Kahle K. Multiomic analyses implicate a neurodevelopmental program in the pathogenesis of cerebral arachnoid cysts. Nature Medicine 2023, 29: 667-678. PMID: 36879130, DOI: 10.1038/s41591-023-02238-2.Peer-Reviewed Original ResearchConceptsArachnoid cystCerebral arachnoid cystsDe novo variantsAC pathogenesisDevelopmental brain lesionsStructural brain diseaseAppropriate clinical contextPatients' medical recordsDamaging de novo variantsMedical recordsClinical severityBrain lesionsHealthy individualsAC subtypesBrain diseasesGenetic testingNeurodevelopmental pathologyClinical contextPathogenesisPatient phenotypesNeurodevelopmental programsNovo variantsRNA sequencing transcriptomeHuman brainCysts