%0 Journal Article
%T Loss-of-Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility
%A Ange-Line Bruel
%A Arnaud Blanchard
%A Arnauld Delarue
%A Aur¨¦lie Bourchany
%A Bertrand Roquelaure
%A Caroline Lacoste
%A Catherine Badens
%A Catherine Guettier-Bouttier
%A Christel Thauvin-Robinet
%A Clothilde Esteve
%A C¨¦cile De Leusse
%A C¨¦line Brochier-Armanet
%A Emmanuel Gonzales
%A Emmanuelle Ecochard-Dugelay
%A Evelyne Marinier
%A Fr¨¦d¨¦ric Huet
%A G¨¦raldine Hery
%A Jacques Sarles
%A Jean-Baptiste Rivi¨¨re
%A Jean-Pierre Hugot
%A Julien Thevenon
%A Karin Mazodier
%A Laurence Faivre
%A Ludmila Francescatto
%A Mina Komuta
%A Nicholas Katsanis
%A Nicolas Levy
%A Olivier Goulet
%A Patrice Bourgeois
%A Perciliz L. Tan
%A Philippe Gauchez
%A Raphaelle Maudinas
%A Sabine Sigaudy
%A Xavier Stephenne
%A Yannis Duffourd
%A Yves Rimet
%J Archive of "American Journal of Human Genetics".
%D 2018
%R 10.1016/j.ajhg.2018.01.009
%X 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
%K GCUNC-45
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985364/