Citations 2
DDX3X syndrome: a multicenter genotype-phenotype study
Coci, Emanuele G. , Millan, Pilar Chacon, ́Agostino, Maria Daniela D, Russell, Laura, Benamor, Mohammed Larbi , Domingo, Ana Jiménez de , Nosková, Lenka , Chapman, Kimberly A. , El‐Hattab, Ayman W. , McLeod, Scott , López‐González, Vanesa , Spataro, Nino , Manso, Carmen, Srour, Myriam , Alsubhi, Sarah, Renaud, Deborah L. , Baethmann, Martina , Wagner, Mathias, Rosenfeld, Jill A., Ahmed, Syed A. , Rawson, Kristyn L., Joensen, Fróði, Tessarech, Marine, Proteau, Clement, Hashemi‐Gorji, Feyzollah , Chatron, Nicolas, Laffargue, Fanny , Pironi, Virginia , Tania, Cruz Marino, Ricard, Jessica, Hammer, Trine Bjørg , Mariani, Milena , Torella, Annalaura, Morleo, Manuela, El-Hattab, Ayman W , Gertzen, Christoph G. W. , Millan, Pilar Chacon , Amor, Mouna Ben , Fernández‐Jaén, Alberto , Magner, Martin , Parikh, Sumit , Goel, Himanshu , Bertini, Enrico , Zanni, Ginevra , Khan, Arif , Amor, David J. , Innes, A. Micheil , Ballesta‐Martínez, María Juliana , Piccione, Maria , Salzano, Emanuela , Wagner, Mathias, Prieto‐Matos, Pablo , Rosenfeld, Jill A. , Scott, Daryl A , Tessarech, Marine , Li, Hong , Michelson, David Joshua , Putoux, Audrey , Chatron, Nicolas , Creveaux, Isabelle , Jamra, Rami Abou , Esch, Hilde Van , Ricard, Jessica, Valenzuela, Irene , Lasa‐Aranzasti, Amaia , Cueto‐González, Anna M. , Reina, Purificación Marín , Martı́nez, Francisco , Ciaccio, Claudia , D’Arrigo, Stefano , Torella, Annalaura , Nigro, Vincenzo , Morleo, Manuela , Østergaard, Elsebet , Gohlke, Holger , Palomares‐Bralo, María , Santos Simarro, Fernando
No container title available | November 11, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract DDX3X dysfunction causes an X-linked multisystem disorder with high penetrance and variable expressivity. The phenotypic spectrum spans from learning disability without somatic involvement to profound intellectual disability with severe impairments in the central nervous system and other organs. A few multicenter studies and single case reports have previously highlighted some common phenotypic patterns but were unable to delineate correlations between underlying DDX3X variants and phenotypic findings.From the second largest patient cohort published to date, we analysed clinical, psychometric and diagnostic findings of 52 female and 7 male individuals, harbouring de novo and inherited DDX3X variants. These female patients revealed previously unknown quantitative correlations between variant type and localization and specific phenotypic findings (growth features, epilepsy, brain anomalies, dysmorphisms, motor-focused neurological findings). Moreover, by analysing the in silico folding and RNA binding capability of mutant DDX3X monomers, we were able to delineate novel correlations between DDX3X monomer misfolding grade and phenotypic severity.
De novo coding variants in the AGO1 gene cause a neurodevelopmental disorder with intellectual disability
Schalk, Audrey , Cousin, Margot A. , Dsouza, Nikita R., Challman, Thomas D. , Wain, Karen E. , Powis, Zöe , Minks, Kelly Q., Trimouille, Aurélien , Lasseaux, Eulalie , Michaud, Vincent , Van‐Gils, Julien , Spataro, Nino , Gabau, Elizabeth, Stolerman, Elliot , Washington, Camerun , Louie, Ray, Lanpher, Brendan C. , Kemppainen, Jennifer L., Innes, Micheil, Kooy, R. Frank , Goldenberg, Alice, Lecoquierre, François , Vera, Gabriella , Sheidley, Beth Rosen , Achkar, Christelle Moufawad El , Park, Meredith, Hamdan, Fadi F. , Michaud, Jacques L. , Lewis, Ann J., Zweier, Christiane , Wagner, Matias , Weigand, Heike, Journel, Hubert, Keren, Boris , Passemard, Sandrine , Mignot, Cyril , Brilstra, Eva H. , Itzikowitz, Gina, O’Heir, Emily , Allen, Jake, Donald, Kirsten A. , Korf, Bruce R. , Skelton, Tammi, Rudy, Natasha L. , Dobyns, William B. , Foss, Kimberly , Bosanko, Katherine A. , Alembik, Yves, Durand, Benjamin , Mau‐Them, Frédéric Tran , Ranza, Emmanuelle , Blanc, Xavier , Torti, Erin , Millan, Francisca , Dameron, Amy, Tokita, Mari, Zimmermann, Michael T. , Klee, Eric W. , Piton, Amélie , Gérard, Bénédicte , Ruiz, Anna , Stolerman, Elliot , Kooy, Frank , Lecoquierre, Francois , Reis, André , Wagner, Matias , Passemard, Sandrine , Tran Mau-Them, Frederic , Klee, Eric W , Piton, Amelie , Zimmermann, Michael T , Lacombe, Didier , Angelini, Chloé , Louie, Raymond J. , Meuwissen, Marije E. C. , Goldenberg, Alice , Diderich, Karin E. M. , Reis, André , Gassen, Koen L.I. van , Thompson, Michelle L. , Robin, Nathaniel H. , Zárate, Yuri A. , Antonarakis, Stylianos E. , McWalter, Kirsty
Journal of Medical Genetics | December 20, 2021 | Volume: 59 | Issue: 10 | Pages: 965-975
Background High-impact pathogenic variants in more than a thousand genes are involved in Mendelian forms of neurodevelopmental disorders (NDD). Methods This study describes the molecular and clinical characterisation of 28 probands with NDD harbouring heterozygous AGO1 coding variants, occurring de novo for all those whose transmission could have been verified (26/28). Results A total of 15 unique variants leading to amino acid changes or deletions were identified: 12 missense variants, two in-frame deletions of one codon, and one canonical splice variant leading to a deletion of two amino acid residues. Recurrently identified variants were present in several unrelated individuals: p.(Phe180del), p.(Leu190Pro), p.(Leu190Arg), p.(Gly199Ser), p.(Val254Ile) and p.(Glu376del). AGO1 encodes the Argonaute 1 protein, which functions in gene-silencing pathways mediated by small non-coding RNAs. Three-dimensional protein structure predictions suggest that these variants might alter the flexibility of the AGO1 linker domains, which likely would impair its function in mRNA processing. Affected individuals present with intellectual disability of varying severity, as well as speech and motor delay, autistic behaviour and additional behavioural manifestations. Conclusion Our study establishes that de novo coding variants in AGO1 are involved in a novel monogenic form of NDD, highly similar to the recently reported AGO2 -related NDD.