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@ARTICLE{Banks:271721,
author = {Banks, Emily and Francis, Vincent and Lin, Sheng-Jia and
Kharfallah, Fares and Fonov, Vladimir and Lévesque, Maxime
and Han, Chanshuai and Kulasekaran, Gopinath and Tuznik,
Marius and Bayati, Armin and Al-Khater, Reem and Alkuraya,
Fowzan S and Argyriou, Loukas and Babaei, Meisam and Bahlo,
Melanie and Bakhshoodeh, Behnoosh and Barr, Eileen and
Bartik, Lauren and Bassiony, Mahmoud and Bertrand, Miriam
and Braun, Dominique and Buchert, Rebecca and Budetta, Mauro
and Cadieux-Dion, Maxime and Calame, Daniel G and Cope,
Heidi and Cushing, Donna and Efthymiou, Stephanie and
Elmaksoud, Marwa Abd and El Said, Huda G and Froukh, Tawfiq
and Gill, Harinder K and Gleeson, Joseph G and Gogoll, Laura
and Goh, Elaine S-Y and Gowda, Vykuntaraju K and Haack,
Tobias B and Hashem, Mais O and Hauser, Stefan and Hoffman,
Trevor L and Hogue, Jacob S and Hosokawa, Akimoto and
Houlden, Henry and Huang, Kevin and Huynh, Stephanie and
Karimiani, Ehsan G and Kaulfuß, Silke and Korenke, G
Christoph and Kritzer, Amy and Lee, Hane and Lupski, James R
and Marco, Elysa J and McWalter, Kirsty and Minassian,
Arakel and Minassian, Berge A and Murphy, David and
Neira-Fresneda, Juanita and Northrup, Hope and Nyaga, Denis
M and Oehl-Jaschkowitz, Barbara and Osmond, Matthew and
Person, Richard and Pehlivan, Davut and Petree, Cassidy and
Sadleir, Lynette G and Saunders, Carol and Schoels, Ludger
and Shashi, Vandana and Spillmann, Rebecca C and Srinivasan,
Varunvenkat M and Torbati, Paria N and Tos, Tulay and Zaki,
Maha S and Zhou, Dihong and Zweier, Christiane and Trempe,
Jean-François and Durcan, Thomas M and Gan-Or, Ziv and
Avoli, Massimo and Alves, Cesar and Varshney, Gaurav K and
Maroofian, Reza and Rudko, David A and McPherson, Peter S},
collaboration = {Network, Undiagnosed Diseases},
othercontributors = {Cope, Heidi},
title = {{L}oss of symmetric cell division of apical neural
progenitors drives {DENND}5{A}-related developmental and
epileptic encephalopathy.},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DZNE-2024-01073},
pages = {7239},
year = {2024},
abstract = {Developmental and epileptic encephalopathies (DEEs) feature
altered brain development, developmental delay and seizures,
with seizures exacerbating developmental delay. Here we
identify a cohort with biallelic variants in DENND5A,
encoding a membrane trafficking protein, and develop animal
models with phenotypes like the human syndrome. We
demonstrate that DENND5A interacts with Pals1/MUPP1,
components of the Crumbs apical polarity complex required
for symmetrical division of neural progenitor cells. Human
induced pluripotent stem cells lacking DENND5A fail to
undergo symmetric cell division with an inherent propensity
to differentiate into neurons. These phenotypes result from
misalignment of the mitotic spindle in apical neural
progenitors. Cells lacking DENND5A orient away from the
proliferative apical domain surrounding the ventricles,
biasing daughter cells towards a more fate-committed state,
ultimately shortening the period of neurogenesis. This study
provides a mechanism for DENND5A-related DEE that may be
generalizable to other developmental conditions and provides
variant-specific clinical information for physicians and
families.},
keywords = {Neural Stem Cells: metabolism / Neural Stem Cells: cytology
/ Humans / Animals / Cell Division / Induced Pluripotent
Stem Cells: metabolism / Induced Pluripotent Stem Cells:
cytology / Mice / Neurogenesis: genetics / Male / Female /
Membrane Proteins: metabolism / Membrane Proteins: genetics
/ Guanine Nucleotide Exchange Factors: metabolism / Guanine
Nucleotide Exchange Factors: genetics / Disease Models,
Animal / Cell Polarity / Membrane Proteins (NLM Chemicals) /
Guanine Nucleotide Exchange Factors (NLM Chemicals)},
cin = {AG Schöls / AG Hauser},
ddc = {500},
cid = {I:(DE-2719)5000005 / I:(DE-2719)1210016},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 352 -
Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39174524},
pmc = {pmc:PMC11341845},
doi = {10.1038/s41467-024-51310-z},
url = {https://pub.dzne.de/record/271721},
}