| Literature DB >> 29429573 |
Clothilde Esteve1, Ludmila Francescatto2, Perciliz L Tan3, Aurélie Bourchany4, Cécile De Leusse5, Evelyne Marinier6, Arnaud Blanchard1, Patrice Bourgeois7, Céline Brochier-Armanet8, Ange-Line Bruel9, Arnauld Delarue5, Yannis Duffourd10, Emmanuelle Ecochard-Dugelay6, Géraldine Hery5, Frédéric Huet11, Philippe Gauchez5, Emmanuel Gonzales12, Catherine Guettier-Bouttier13, Mina Komuta14, Caroline Lacoste15, Raphaelle Maudinas11, Karin Mazodier16, Yves Rimet17, Jean-Baptiste Rivière9, Bertrand Roquelaure5, Sabine Sigaudy18, Xavier Stephenne19, Christel Thauvin-Robinet10, Julien Thevenon9, Jacques Sarles5, Nicolas Levy7, Catherine Badens7, Olivier Goulet20, Jean-Pierre Hugot6, Nicholas Katsanis3, Laurence Faivre10, Alexandre Fabre21.
Abstract
Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing, and bone fragility. Whole-exome sequencing of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A) as a likely driver for this disorder. Subsequent in vitro and in vivo functional studies of the candidate gene indicated a loss-of-function paradigm, wherein mutations attenuated or abolished protein activity with concomitant defects in gut development and function.Entities:
Keywords: GCUNC-45
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Substances：
Year: 2018 PMID： 29429573 PMCID： PMC5985364 DOI： 10.1016/j.ajhg.2018.01.009
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025