Shujuan Zhao, Kedous Y Mekbib, Martijn A van der Ent, Garrett Allington, Andrew Prendergast, Jocelyn E Chau, Hannah Smith, John Shohfi, Jack Ocken, Daniel Duran, Charuta G Furey, Hao Thi Le, Phan Q Duy, Benjamin C Reeves, Junhui Zhang, Carol Nelson-Williams, Di Chen, Boyang Li, Timothy Nottoli, Suxia Bai, Myron Rolle, Xue Zeng, Weilai Dong, Po-Ying Fu, Yung-Chun Wang, Shrikant Mane, Paulina Piwowarczyk, Katie Pricola Fehnel, Alfred Pokmeng See, Bermans J Iskandar, Beverly Aagaard-Kienitz, Adam J Kundishora, Tyrone DeSpenza, Ana B W Greenberg, Seblewengel M Kidanemariam, Andrew T Hale, James M Johnston, Eric M Jackson, Phillip B Storm, Shih-Shan Lang, William E Butler, Bob S Carter, Paul Chapman, Christopher J Stapleton, Aman B Patel, Georges Rodesch, Stanislas Smajda, Alejandro Berenstein, Tanyeri Barak, E Zeynep Erson-Omay, Hongyu Zhao, Andres Moreno-De-Luca, Mark R Proctor, Edward R Smith, Darren B Orbach, Seth L Alper, Stefania Nicoli, Titus J Boggon, Richard P Lifton, Murat Gunel, Philip D King, Sheng Chih Jin, Kristopher T Kahle
To elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and severe congenital brain arteriovenous malformation, we performed an integrated analysis of 310 VOGM proband-family exomes and 336,326 human cerebrovasculature single-cell transcriptomes. We found the Ras suppressor p120 RasGAP ( RASA1 ) harbored a genome-wide significant burden of loss-of-function de novo variants (p=4.79×10 -7 ). Rare, damaging transmitted variants were enriched in Ephrin receptor-B4 ( EPHB4 ) (p=1...
March 21, 2023: bioRxiv