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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Biallelic Variants in UBA5 Reveal that Disruption of the UFM1 Cascade Can Result in Early-Onset Encephalopathy
American Journal of Human Genetics, Volume 99, No. 3, Year 2016
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Description
Via whole-exome sequencing, we identified rare autosomal-recessive variants in UBA5 in five children from four unrelated families affected with a similar pattern of severe intellectual deficiency, microcephaly, movement disorders, and/or early-onset intractable epilepsy. UBA5 encodes the E1-activating enzyme of ubiquitin-fold modifier 1 (UFM1), a recently identified ubiquitin-like protein. Biochemical studies of mutant UBA5 proteins and studies in fibroblasts from affected individuals revealed that UBA5 mutations impair the process of ufmylation, resulting in an abnormal endoplasmic reticulum structure. In Caenorhabditis elegans, knockout of uba-5 and of human orthologous genes in the UFM1 cascade alter cholinergic, but not glutamatergic, neurotransmission. In addition, uba5 silencing in zebrafish decreased motility while inducing abnormal movements suggestive of seizures. These clinical, biochemical, and experimental findings support our finding of UBA5 mutations as a pathophysiological cause for early-onset encephalopathies due to abnormal protein ufmylation. © 2016 American Society of Human Genetics
Authors & Co-Authors
Colin, Estelle
France, Angers
Chu Angers
France, Angers
Université D’angers
Ziegler, Alban
France, Angers
Chu Angers
France, Angers
Université D’angers
Haack, Tobias Bernd
Germany, Munich
Technische Universität München
Khiati, Salim
France, Angers
Université D’angers
Amati-Bonneau, Patrizia
France, Angers
Chu Angers
France, Angers
Université D’angers
Charif, Majida
France, Angers
Université D’angers
Procaccio, Vincent
France, Angers
Chu Angers
France, Angers
Université D’angers
Reynier, Pascal
France, Angers
Chu Angers
France, Angers
Université D’angers
Aleck, Kyrieckos A.
Unknown Affiliation
Botto, Lorenzo D.
United States, Salt Lake City
The University of Utah
Nabbout, Rima C.
France, Paris
Hôpital Necker Enfants Malades
Assmann, Birgit E.
Germany, Heidelberg
Universitätsklinikum Heidelberg
Meitinger, Thomas A.
Germany, Munich
Technische Universität München
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Strom, Tim Matthias
Germany, Munich
Technische Universität München
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Prokisch, Holger
Germany, Munich
Technische Universität München
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Geńin, Emmanuelle
Unknown Affiliation
Campion, Dominique
Unknown Affiliation
Dartigues, Jean François
Unknown Affiliation
Deleuze, Jean François
Unknown Affiliation
Lambert, Jean Charles
Unknown Affiliation
Redon, Richard
Unknown Affiliation
Ludwig, Thomas E.
Unknown Affiliation
Grenier-Boley, Benjamin
Unknown Affiliation
Lindenbaum, Pierre
Unknown Affiliation
Meyer, Vincent
Unknown Affiliation
Dina, Christian
Unknown Affiliation
Bellenguez, Céline
Unknown Affiliation
Giemza, Joanna
Unknown Affiliation
Chatel, Stéphanie
Unknown Affiliation
Féréc, Claude F.
Unknown Affiliation
Le Maréc, Hervé
Unknown Affiliation
Letenneur, L.
Unknown Affiliation
Nicolas, Gaël
Unknown Affiliation
Rouault, Karen
Unknown Affiliation
Bacq-Daian, Delphine
Unknown Affiliation
Boland, Anne
Unknown Affiliation
Lechner, Doris
Unknown Affiliation
Hoffmann, Georg Friedrich
Germany, Heidelberg
Universitätsklinikum Heidelberg
Lenaers, Guy
France, Angers
Université D’angers
Bomont, Pascale
France, Montpellier
Institut Des Neurosciences de Montpellier
Liebau, Eva
Germany, Munster
University of Münster
Bonneau, Dominique
France, Angers
Chu Angers
France, Angers
Université D’angers
Statistics
Citations: 75
Authors: 42
Affiliations: 10
Identifiers
Doi:
10.1016/j.ajhg.2016.06.030
ISSN:
00029297
Research Areas
Genetics And Genomics
Maternal And Child Health