PUBLICATION
Loss-of-Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility
- Authors
- 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., Lacoste, C., Maudinas, R., Mazodier, K., Rimet, Y., Rivière, J.B., Roquelaure, B., Sigaudy, S., Stephenne, X., Thauvin-Robinet, C., Thevenon, J., Sarles, J., Levy, N., Badens, C., Goulet, O., Hugot, J.P., Katsanis, N., Faivre, L., Fabre, A.
- ID
- ZDB-PUB-181212-31
- Date
- 2018
- Source
- American journal of human genetics 102: 364-374 (Journal)
- Registered Authors
- Francescatto, Ludmila, Katsanis, Nicholas
- Keywords
- GCUNC-45
- MeSH Terms
-
- Adolescent
- Animals
- Bone and Bones/pathology*
- Child, Preschool
- Cholestasis/genetics*
- Diarrhea/genetics*
- Diarrhea/physiopathology
- Family
- Female
- Fibroblasts/pathology
- Gastrointestinal Motility
- Hearing Loss/genetics*
- Humans
- Infant, Newborn
- Intracellular Signaling Peptides and Proteins/genetics*
- Loss of Function Mutation/genetics*
- Lymphocytes/pathology
- Male
- Pedigree
- Phenotype
- Syndrome
- Young Adult
- Zebrafish
- PubMed
- 29429573 Full text @ Am. J. Hum. Genet.
Citation
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., Lacoste, C., Maudinas, R., Mazodier, K., Rimet, Y., Rivière, J.B., Roquelaure, B., Sigaudy, S., Stephenne, X., Thauvin-Robinet, C., Thevenon, J., Sarles, J., Levy, N., Badens, C., Goulet, O., Hugot, J.P., Katsanis, N., Faivre, L., Fabre, A. (2018) Loss-of-Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility. American journal of human genetics. 102:364-374.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping