Author(s)
Charles J. Sheehan
Published 1 Project
Genetics Corpus Callosum Agenesis Ddx3X Helicase Radial Glial
Kimberly A Aldinger
Published 2 Projects
Biochemistry Genetics Corpus Callosum Agenesis Ddx3X Helicase
Dusica Babovic-Vuksanovic
Published 1 Project
Genetics Corpus Callosum Agenesis Ddx3X Helicase Radial Glial
Stéphane Bézieau
Published 3 Projects
Genetics Genetic And Genomic Medicine Distal Genetic Risk Factors Genetic Heterogeneity
Patrick R. Blackburn
Published 1 Project
Genetics Corpus Callosum Agenesis Ddx3X Helicase Radial Glial
Nataliya Di Donato
Published 1 Project
Genetics Corpus Callosum Agenesis Ddx3X Helicase Radial Glial
Bethany L. Johnson-Kerner
Published 1 Project
Genetics Corpus Callosum Agenesis Ddx3X Helicase Radial Glial
Sébastien Küry
Published 4 Projects
Genetics Genetic And Genomic Medicine Distal Genetic Risk Factors Genetic Heterogeneity
Dominique Martin-Coignard
Published 1 Project
Genetics Corpus Callosum Agenesis Ddx3X Helicase Radial Glial
Christel Thauvin-Robinet
Published 1 Project
Genetics Corpus Callosum Agenesis Ddx3X Helicase Radial Glial
A. James Barkovich
Published 2 Projects
Genetics Corpus Callosum Agenesis Ddx3X Helicase Radial Glial
Content
De novo germline mutations in the RNA helicase DDX3X account for 1-3% of unexplained intellectual disability (ID) cases in females, and are associated with autism, brain malformations, and epilepsy. Yet, the developmental and molecular mechanisms by which DDX3X mutations impair brain function are unknown. Here we use human and mouse genetics, and cell biological and biochemical approaches to elucidate mechanisms by which pathogenic DDX3X variants disrupt brain development. We report the largest clinical cohort to date with DDX3X mutations (n=78), demonstrating a striking correlation between recurrent dominant missense mutations, polymicrogyria, and the most severe clinical outcomes. We show that Ddx3x controls cortical development by regulating neuronal generation and migration. Severe DDX3X missense mutations profoundly disrupt RNA helicase activity and induce ectopic RNA-protein granules and aberrant translation in neural progenitors and neurons. Together, our study demonstrates novel mechanisms underlying DDX3X syndrome, and highlights roles for RNA-protein aggregates in the pathogenesis of neurodevelopmental disease.
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Sébastien Küry. (2021, Nov 4).Pathogenic DDX3X mutations impair RNA metabolism and neurogenesis during fetal cortical development[Video]. Scitok. https://scitok.com/project/p/4a2b23d3
L. Lennox Ashley. "Pathogenic DDX3X mutations impair RNA metabolism and neurogenesis during fetal cortical development" Scitok, uploaded by Küry Sébastien, 4 Nov, 2021, https://scitok.com/project/p4a2b23d3
Sébastien Küry. "Pathogenic DDX3X mutations impair RNA metabolism and neurogenesis during fetal cortical development" Scitok. (Nov 4, 2021). https://scitok.com/project/p/4a2b23d3
Sébastien Küry (Nov 4, 2021). Pathogenic DDX3X mutations impair RNA metabolism and neurogenesis during fetal cortical development Scitok. https://scitok.com/project/p/4a2b23d3
Sébastien Küry. Pathogenic DDX3X mutations impair RNA metabolism and neurogenesis during fetal cortical development[video]. 2021 Nov 4. https://scitok.com/project/p/4a2b23d3
@online{al2006link, title={ Pathogenic DDX3X mutations impair RNA metabolism and neurogenesis during fetal cortical development }, author={ Küry, Sébastien }, organization={Scitok}, month={ Nov }, day={ 4 }, year={ 2021 }, url = {https://scitok.com/project/p/4a2b23d3}, }