Loss-of-Function Mutations inUNC45ACause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility
(2018) American Journal of Human Genetics — Vol. 102, n° 3, p. 364-374 (2018)
Files
2018_Esteve_Am_J_Hum_Genet.pdf
PMC
Open Access - Adobe PDF
- 2.03 MB
Details
- Authors
- 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.
- Affiliations
Citations
Esteve, C., Francescatto, L., Tan, P. L., Bourchany, A., De Leusse, C., Marinier, E., Blanchard, A., Bourgeois, P., Brochier-Armanet, C., Bruel, A.-L., Delarue, A., Duffourd, Y., Ecochard-Dugelay, E., Hery, G., Huet, F., Gauchez, P., Gonzales, E., Guettier-Bouttier, C., Komuta, M., et al. (2018). Loss-of-Function Mutations inUNC45ACause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility. American Journal of Human Genetics, 102(3), 364-374. https://doi.org/10.1016/j.ajhg.2018.01.009 (Original work published 2018)