| Literature DB >> 29100085 |
Davor Lessel1, Claudia Schob2, Sébastien Küry3, Margot R F Reijnders4, Tamar Harel5, Mohammad K Eldomery6, Zeynep Coban-Akdemir6, Jonas Denecke7, Shimon Edvardson8, Estelle Colin9, Alexander P A Stegmann10, Erica H Gerkes11, Marine Tessarech9, Dominique Bonneau9, Magalie Barth9, Thomas Besnard3, Benjamin Cogné3, Anya Revah-Politi12, Tim M Strom13, Jill A Rosenfeld6, Yaping Yang6, Jennifer E Posey6, LaDonna Immken14, Nelly Oundjian15, Katherine L Helbig16, Naomi Meeks17, Kelsey Zegar17, Jenny Morton18, Jolanda H Schieving19, Ana Claasen20, Matthew Huentelman20, Vinodh Narayanan20, Keri Ramsey20, Han G Brunner4, Orly Elpeleg21, Sandra Mercier3, Stéphane Bézieau3, Christian Kubisch22, Tjitske Kleefstra4, Stefan Kindler2, James R Lupski23, Hans-Jürgen Kreienkamp24.
Abstract
DHX30 is a member of the family of DExH-box helicases, which use ATP hydrolysis to unwind RNA secondary structures. Here we identified six different de novo missense mutations in DHX30 in twelve unrelated individuals affected by global developmental delay (GDD), intellectual disability (ID), severe speech impairment and gait abnormalities. While four mutations are recurrent, two are unique with one affecting the codon of one recurrent mutation. All amino acid changes are located within highly conserved helicase motifs and were found to either impair ATPase activity or RNA recognition in different in vitro assays. Moreover, protein variants exhibit an increased propensity to trigger stress granule (SG) formation resulting in global translation inhibition. Thus, our findings highlight the prominent role of translation control in development and function of the central nervous system and also provide molecular insight into how DHX30 dysfunction might cause a neurodevelopmental disorder.Entities:
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Year: 2017 PMID： 29100085 PMCID： PMC5673606 DOI： 10.1016/j.ajhg.2017.09.014
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025