Bruel, Ange-Line
Mayo Clinic
Génétique des Anomalies du Développement (GAD), UMR 1231, INSERM, Université Bourgogne-Franche Comté, Dijon, France.
Citations 2
Germline mutations in a G protein identify signaling cross-talk in T cells
Ham, Hyoungjun , Jing, Huie , Lamborn, Ian T. , Kober, M. , Anderson, David E. , Druey, Kirk M. , Mandl, Judith N. , Isidor, Bertrand , Freeman, Alexandra F. , Ganesan, Sundar , Karsak, Meliha , Mustillo, Peter , Teo, Juliana , Zolkipli‐Cunningham, Zarazuela , Lecoquierre, François , Schmid, Jana Pachlopnik , Kuhns, Douglas B. , Xu, Xuehua , Al–Herz, Waleed , Terhal, Paulien A., Muurinen, Mari , Barlogis, Vincent , Danielson, Jeffrey J. , Stewart, Helen , Rading, Sebastian, Keren, Boris , Pfundt, Rolph , Potocki, Lorraine , Olivier, Kenneth N., Faivre, Laurence , Wong, Melanie , Puel, Anne , Chou, Janet , Tusseau, Maud, Moutsopoulos, Niki M. , Matthews, Helen, Simons, Cas , Fink, Danielle , Kong, Heidi H. , Kabát, Juraj , Kim, Woo Sung , Bierhals, Tatjana , Meguro, Kazuyuki , Gu, Jingwen , Stoddard, Jennifer , Banos-Pinero, Benito, Slack, Maria A., Trivellin, Giampaolo , Mazel, Benoît , Li, Samuel T. , Watts, Val J. , Rodriguez-Quevedo, Maria F. , Bruel, Ange‐Line , Lehalle, Daphné , Torres, Daniel , Sullivan, Kathleen E. , Duffourd, Yannis, Similuk, Morgan , Blanc, Pierre , Jin, Tian, Geha, Raif S., Casanova, Jean‐Laurent , Mäkitie, Outi , Edery, Patrick , Germain, Ronald N. , Billadeau, Daniel D. , Zhang, Yu , Lenardo, Michael J. , Kober, Megan M , Koval, Alexey , Anderson, D Eric , Druey, Kirk M , Mandl, Judith N , Isidor, Bertrand , Ferreira, Carlos R , Freeman, Alexandra F , Karsak, Meliha , Mustillo, Peter J , Teo, Juliana , Chatron, Nicolas , Lecoquierre, Francois , Oler, Andrew J , Schmid, Jana Pachlopnik , Kuhns, Douglas B , Xu, Xuehua , Hauck, Fabian , Al-Herz, Waleed , Wagner, Matias , Terhal, Paulien A , Muurinen, Mari , Barlogis, Vincent , Loid, Petra , Keren, Boris , Pfundt, Rolph , Zarember, Kol A , Vill, Katharina , Olivier, Kenneth N , Lesca, Gaetan , Faivre, Laurence , Puel, Anne , Chou, Janet , Moutsopoulos, Niki M , Simons, Cas , Soldatos, Ariane , Masle-Farquhar, Etienne , Pittaluga, Stefania , Brink, Robert , Kong, Heidi H , Kabat, Juraj , Bierhals, Tatjana , Hsu, Amy P. , Gu, Jingwen , Trivellin, Giampaolo , Mazel, Benoît , Soomann, Maarja , Li, Samuel , Watts, Val J , Stratakis, Constantine A , Rodriguez-Quevedo, Maria F , Bruel, Ange-Line , Lipsanen-Nyman, Marita , Saultier, Paul , Lehalle, Daphne , Torres, Daniel , Barbarot, Sébastien , Neu, Axel , Similuk, Morgan N , McWalter, Kirsty , Blanc, Pierre , Bézieau, Stéphane , Geha, Raif S , Casanova, Jean Laurent , Makitie, Outi M , Edery, Patrick , Christodoulou, John , Germain, Ronald N , Goodnow, Christopher C , Sakmar, Thomas P , Billadeau, Daniel D , Kury, Sebastien , Katanaev, Vladimir L , Zhang, Yu , Lenardo, Michael J , Su, Helen C , Berchiche, Yamina A. , Wagner, Matias , Cruz, Phillip , Lesca, Gaëtan , Tusseau, Maud , Taft, Ryan J. , Pittaluga, Stefania , Baños-Piñero, Benito, Stratakis, Constantine A. , Jain, Rashmi, Bezieau, Stéphane , Jin, Tian , Kubisch, Christian , Küry, Sébastien , Su, Helen C.
Science | September 19, 2024 | Volume: 385 | Issue: 6715 | Pages: No page available
Humans with monogenic inborn errors responsible for extreme disease phenotypes can reveal essential physiological pathways. We investigated germline mutations in GNAI2 , which encodes G αi2 , a key component in heterotrimeric G protein signal transduction usually thought to regulate adenylyl cyclase–mediated cyclic adenosine monophosphate (cAMP) production. Patients with activating G αi2 mutations had clinical presentations that included impaired immunity. Mutant G αi2 impaired cell migration and augmented responses to T cell receptor (TCR) stimulation. We found that mutant G αi2 influenced TCR signaling by sequestering the guanosine triphosphatase (GTPase)–activating protein RASA2, thereby promoting RAS activation and increasing downstream extracellular signal–regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)–AKT S6 signaling to drive cellular growth and proliferation.
Expanding the phenotype of ASXL3‐related syndrome: A comprehensive description of 45 unpublished individuals with inherited and de novo pathogenic variants in ASXL3
Schirwani, Schaida , Albaba, Shadi , Carere, Deanna Alexis , Sacoto, María J. Guillen , Zamora, Francisca Milan, Si, Yue , Rabin, Rachel , Renaud, Deborah L. , Hauser, Natalie , Blanchet, Patricia, Foulds, Nichola, Dixit, Abhijit , Fisher, Richard, Armstrong, Ruth, Isidor, Bertrand , Demirdas, Serwet , Dykzeul, Natalie, Cohen, Julie S. , Grand, Katheryn , Swols, Dayna Morel , Albassam, Hessa F., Naik, Swati , Ragge, Nicola , Tedesco, Maria Giovanna , Harrison, Rachel , Bouman, Arjan , Palen, Emily, Challman, Thomas D. , Willemsen, Marjolein H. , Vogt, Julie , Cunniff, Christopher , Bergstrom, Katherine , Bruel, Ange‐Line , Kini, Usha , Alkuraya, Fowzan S. , Slegesky, Valerie, Meeks, Naomi, Girotto, Paula Natale , Johnson, Diana , Study, DDD, Newbury‐Ecob, Ruth , Lynch, Sally Ann , Graham, John M. , Balasubramanian, Meena , Hauser, Natalie , Schrier Vergano, Samantha , Bouman, Arjan , Cunniff, Christopher , Bergstrom, Katherine , Bruel, Ange-Line , Alkuraya, Fowzan S , Prontera, Paolo , Li, Dong , Graham, John M , Zamora, Francisca Millan, Pappas, John , Reid, Evan , Cogné, Benjamin , Vergano, Samantha A. Schrier , Slavotinek, Anne , Naik, Swati, Dean, John , Costa, Cinzia , Walia, Jagdeep Singh , Study, DDD, Ockeloen, Charlotte W. , Li, Dong , Pierson, Tyler Mark
American Journal of Medical Genetics Part A | August 26, 2021 | Volume: 185 | Issue: 11 | Pages: 3446-3458
AbstractThe study aimed at widening the clinical and genetic spectrum of ASXL3‐related syndrome, a neurodevelopmental disorder, caused by truncating variants in the ASXL3 gene. In this international collaborative study, we have undertaken a detailed clinical and molecular analysis of 45 previously unpublished individuals with ASXL3‐related syndrome, as well as a review of all previously published individuals. We have reviewed the rather limited functional characterization of pathogenic variants in ASXL3 and discuss current understanding of the consequences of the different ASXL3 variants. In this comprehensive analysis of ASXL3‐related syndrome, we define its natural history and clinical evolution occurring with age. We report familial ASXL3 pathogenic variants, characterize the phenotype in mildly affected individuals and discuss nonpenetrance. We also discuss the role of missense variants in ASXL3. We delineate a variable but consistent phenotype. The most characteristic features are neurodevelopmental delay with consistently limited speech, significant neuro‐behavioral issues, hypotonia, and feeding difficulties. Distinctive features include downslanting palpebral fissures, hypertelorism, tubular nose with a prominent nasal bridge, and low‐hanging columella. The presented data will inform clinical management of individuals with ASXL3‐related syndrome and improve interpretation of new ASXL3 sequence variants.