TY - JOUR
T1 - Cohort Expansion and Genotype-Phenotype Analysis of RAB11A-Associated Neurodevelopmental Disorder
AU - Undiagnosed Diseases Network
AU - Borroto, Maria Carla
AU - Patel, Heena
AU - Srivastava, Siddharth
AU - Swanson, Lindsay C.
AU - Keren, Boris
AU - Whalen, Sandra
AU - Mignot, Cyril
AU - Wang, Xiaodong
AU - Chen, Qian
AU - Rosenfeld, Jill A.
AU - McLean, Scott
AU - Littlejohn, Rebecca O.
AU - Acosta, Maria T.
AU - Adam, Margaret
AU - Adams, David R.
AU - Alvarez, Raquel L.
AU - Alvey, Justin
AU - Amendola, Laura
AU - Andrews, Ashley
AU - Ashley, Euan A.
AU - Bacino, Carlos A.
AU - Bademci, Guney
AU - Balasubramanyam, Ashok
AU - Baldridge, Dustin
AU - Bale, Jim
AU - Bamshad, Michael
AU - Barbouth, Deborah
AU - Bayrak-Toydemir, Pinar
AU - Beck, Anita
AU - Beggs, Alan H.
AU - Behrens, Edward
AU - Bejerano, Gill
AU - Bellen, Hugo J.
AU - Bennett, Jimmy
AU - Berg-Rood, Beverly
AU - Bernstein, Jonathan A.
AU - Berry, Gerard T.
AU - Bican, Anna
AU - Bivona, Stephanie
AU - Blue, Elizabeth
AU - Bohnsack, John
AU - Bonner, Devon
AU - Botto, Lorenzo
AU - Boyd, Brenna
AU - Briere, Lauren C.
AU - Brokamp, Elly
AU - Brown, Gabrielle
AU - Burke, Elizabeth A.
AU - Burrage, Lindsay C.
AU - Butte, Manish J.
AU - Byers, Peter
AU - Byrd, William E.
AU - Carey, John
AU - Carrasquillo, Olveen
AU - Cassini, Thomas
AU - Peter Chang, Ta Chen
AU - Chanprasert, Sirisak
AU - Chao, Hsiao Tuan
AU - Clark, Gary D.
AU - Coakley, Terra R.
AU - Cobban, Laurel A.
AU - Cogan, Joy D.
AU - Coggins, Matthew
AU - Cole, F. Sessions
AU - Colley, Heather A.
AU - Cooper, Cynthia M.
AU - Cope, Heidi
AU - Corona, Rosario
AU - Craigen, William J.
AU - Crouse, Andrew B.
AU - Cunningham, Michael
AU - D'Souza, Precilla
AU - Dai, Hongzheng
AU - Dasari, Surendra
AU - Davis, Joie
AU - Dayal, Jyoti G.
AU - Dell'Angelica, Esteban C.
AU - Dipple, Katrina
AU - Doherty, Daniel
AU - Dorrani, Naghmeh
AU - Doss, Argenia L.
AU - Douine, Emilie D.
AU - Duncan, Laura
AU - Earl, Dawn
AU - Eckstein, David J.
AU - Emrick, Lisa T.
AU - Eng, Christine M.
AU - Falk, Marni
AU - Fieg, Elizabeth L.
AU - Fisher, Paul G.
AU - Fogel, Brent L.
AU - Forghani, Irman
AU - Gahl, William A.
AU - Glass, Ian
AU - Gochuico, Bernadette
AU - Goddard, Page C.
AU - Godfrey, Rena A.
AU - Golden-Grant, Katie
AU - Grajewski, Alana
AU - Hadley, Don
AU - Hahn, Sihoun
AU - Halley, Meghan C.
AU - Hamid, Rizwan
AU - Hassey, Kelly
AU - Hayes, Nichole
AU - High, Frances
AU - Hing, Anne
AU - Hisama, Fuki M.
AU - Holm, Ingrid A.
AU - Hom, Jason
AU - Horike-Pyne, Martha
AU - Huang, Alden
AU - Hutchison, Sarah
AU - Introne, Wendy
AU - Isasi, Rosario
AU - Izumi, Kosuke
AU - Jamal, Fariha
AU - Jarvik, Gail P.
AU - Jarvik, Jeffrey
AU - Jayadev, Suman
AU - Jean-Marie, Orpa
AU - Jobanputra, Vaidehi
AU - Karaviti, Lefkothea
AU - Kennedy, Jennifer
AU - Ketkar, Shamika
AU - Kiley, Dana
AU - Kilich, Gonench
AU - Kobren, Shilpa N.
AU - Kohane, Isaac S.
AU - Kohler, Jennefer N.
AU - Korrick, Susan
AU - Kozuira, Mary
AU - Krakow, Deborah
AU - Krasnewich, Donna M.
AU - Kravets, Elijah
AU - Lalani, Seema R.
AU - Lam, Byron
AU - Lam, Christina
AU - Lanpher, Brendan C.
AU - Lanza, Ian R.
AU - LeBlanc, Kimberly
AU - Lee, Brendan H.
AU - Levitt, Roy
AU - Lewis, Richard A.
AU - Liu, Pengfei
AU - Liu, Xue Zhong
AU - Longo, Nicola
AU - Loo, Sandra K.
AU - Loscalzo, Joseph
AU - Maas, Richard L.
AU - Macnamara, Ellen F.
AU - MacRae, Calum A.
AU - Maduro, Valerie V.
AU - Maghiro, Audrey Stephannie
AU - Mahoney, Rachel
AU - Malicdan, May Christine V.
AU - Mamounas, Laura A.
AU - Manolio, Teri A.
AU - Mao, Rong
AU - Maravilla, Kenneth
AU - Marom, Ronit
AU - Marth, Gabor
AU - Martin, Beth A.
AU - Martin, Martin G.
AU - Martínez-Agosto, Julian A.
AU - Marwaha, Shruti
AU - McCauley, Jacob
AU - McConkie-Rosell, Allyn
AU - McCray, Alexa T.
AU - McGee, Elisabeth
AU - Mefford, Heather
AU - Merritt, J. Lawrence
AU - Might, Matthew
AU - Mirzaa, Ghayda
AU - Morava, Eva
AU - Moretti, Paolo
AU - Mulvihill, John
AU - Nakano-Okuno, Mariko
AU - Nelson, Stanley F.
AU - Newman, John H.
AU - Nicholas, Sarah K.
AU - Nickerson, Deborah
AU - Nieves-Rodriguez, Shirley
AU - Novacic, Donna
AU - Oglesbee, Devin
AU - Orengo, James P.
AU - Pace, Laura
AU - Pak, Stephen
AU - Pallais, J. Carl
AU - Palmer, Christina G.S.
AU - Papp, Jeanette C.
AU - Parker, Neil H.
AU - Phillips, John A.
AU - Posey, Jennifer E.
AU - Potocki, Lorraine
AU - Schedl, Timothy
AU - Shin, Jimann
AU - Solnica-Krezel, Lilianna
AU - Wambach, Jennifer
AU - Granadillo, Jorge L.
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/11
Y1 - 2024/11
N2 - Background: GTPases of the Rab family are important orchestrators of membrane trafficking, and their dysregulation has been linked to a variety of neuropathologies. In 2017, we established a causal link between RAB11A variants and developmental and epileptic encephalopathy. In this study, we expand the phenotype of RAB11A-associated neurodevelopmental disorder and explore genotype-phenotype correlations. Methods: We assessed 16 patients with pathogenic or likely pathogenic RAB11A variants, generally de novo, heterozygous missense variants. One individual had a homozygous nonsense variant, although concomitant with a pathogenic LAMA2 variant, which made their respective contributions to the phenotype difficult to discriminate. Results: We reinforce the finding that certain RAB11A missense variants lead to intellectual disability and developmental delays. Other clinical features might include gait disturbances, hypotonia, magnetic resonance imaging abnormalities, visual anomalies, dysmorphisms, early adrenarche, and obesity. Epilepsy seems to be less common and linked to variants outside the binding sites. Individuals with variants in the binding sites seem to have a more multisystemic, nonepileptic phenotype. Conclusions: Similar to other Rab-related disorders, RAB11A-associated neurodevelopmental disorder can also impact gait, tonus, brain anatomy and physiology, vision, adrenarche, and body weight and structure. Epilepsy seems to affect the minority of patients with variants outside the binding sites.
AB - Background: GTPases of the Rab family are important orchestrators of membrane trafficking, and their dysregulation has been linked to a variety of neuropathologies. In 2017, we established a causal link between RAB11A variants and developmental and epileptic encephalopathy. In this study, we expand the phenotype of RAB11A-associated neurodevelopmental disorder and explore genotype-phenotype correlations. Methods: We assessed 16 patients with pathogenic or likely pathogenic RAB11A variants, generally de novo, heterozygous missense variants. One individual had a homozygous nonsense variant, although concomitant with a pathogenic LAMA2 variant, which made their respective contributions to the phenotype difficult to discriminate. Results: We reinforce the finding that certain RAB11A missense variants lead to intellectual disability and developmental delays. Other clinical features might include gait disturbances, hypotonia, magnetic resonance imaging abnormalities, visual anomalies, dysmorphisms, early adrenarche, and obesity. Epilepsy seems to be less common and linked to variants outside the binding sites. Individuals with variants in the binding sites seem to have a more multisystemic, nonepileptic phenotype. Conclusions: Similar to other Rab-related disorders, RAB11A-associated neurodevelopmental disorder can also impact gait, tonus, brain anatomy and physiology, vision, adrenarche, and body weight and structure. Epilepsy seems to affect the minority of patients with variants outside the binding sites.
KW - Epileptic encephalopathy
KW - GTPase
KW - Neurodevelopmental disorder
KW - RAB11
UR - http://www.scopus.com/inward/record.url?scp=85202202805&partnerID=8YFLogxK
U2 - 10.1016/j.pediatrneurol.2024.07.010
DO - 10.1016/j.pediatrneurol.2024.07.010
M3 - Article
C2 - 39181022
AN - SCOPUS:85202202805
SN - 0887-8994
VL - 160
SP - 45
EP - 53
JO - Pediatric Neurology
JF - Pediatric Neurology
ER -