Loss-of-Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility.
Fiche publication
Date publication
mars 2018
Journal
American journal of human genetics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr HUET Frédéric, Pr FAIVRE Laurence
Tous les auteurs :
Esteve C, Francescatto L, Tan PL, Bourchany A, De Leusse C, Marinier E, Blanchard A, Bourgeois P, Brochier-Armanet C, Bruel AL, Delarue A, Duffourd Y, Ecochard-Dugelay E, Hery G, Huet F, Gauchez P, Gonzales E, Guettier-Bouttier C, Komuta M, Lacoste C, Maudinas R, Mazodier K, Rimet Y, Rivière JB, Roquelaure B, Sigaudy S, Stephenne X, Thauvin-Robinet C, Thevenon J, Sarles J, Levy N, Badens C, Goulet O, Hugot JP, Katsanis N, Faivre L, Fabre A
Lien Pubmed
Résumé
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.
Mots clés
GCUNC-45
Référence
Am. J. Hum. Genet.. 2018 Mar 1;102(3):364-374