Osteo-Oto-Hepato-Enteric Syndrome (O2HE) is caused by loss of function mutations in UNC45A

Clothilde Esteve; Ludmila Francescatto; Perciliz L. Tan; Aurélie Bourchany; Cécile de Leusse; Evelyne Marinier; Arnaud Blanchard; Patrice Bourgeois; Céline Brochier-Armanet; Ange Line Bruel; Arnauld Delarue; Yannis Duffourd; Emmanuelle Ecochard-Dugelay; Géraldine Hery; Frédéric Huet; Philippe Gauchez; Emmanuel Gonzales; Catherine Guettier-Bouttier; Mina Komuta; Caroline Lacoste; Raphaelle Maudinas; Karin Mazodier; Yves Rimet; Jean Baptiste Rivière; Bertrand Roquelaure; Sabine Sigaudy; Xavier Stephenne; Christel Thauvin-Robinet; Julien Thevenon; Jacques Sarles; Nicolas Levy; Catherine Badens; Olivier Goulet; Jean Pierre Hugot; Nicholas Katsanis; Laurence Faivre; Alexandre Fabre

doi:10.1101/208942

Osteo-Oto-Hepato-Enteric Syndrome (O2HE) is caused by loss of function mutations in UNC45A

Clothilde Esteve, Ludmila Francescatto, Perciliz L. Tan, Aurélie Bourchany, Cécile de Leusse, Evelyne Marinier, Arnaud Blanchard, Patrice Bourgeois, Céline Brochier-Armanet, Ange Line Bruel, Arnauld Delarue, Yannis Duffourd, Emmanuelle Ecochard-Dugelay, Géraldine Hery, Frédéric Huet, Philippe Gauchez, Emmanuel Gonzales, Catherine Guettier-Bouttier, Mina Komuta, Caroline LacosteRaphaelle Maudinas, Karin Mazodier, Yves Rimet, Jean Baptiste Rivière, Bertrand Roquelaure, Sabine Sigaudy, Xavier Stephenne, Christel Thauvin-Robinet, Julien Thevenon, Jacques Sarles, Nicolas Levy, Catherine Badens, Olivier Goulet, Jean Pierre Hugot, Nicholas Katsanis, Laurence Faivre, Alexandre Fabre^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with hitherto unknown syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing and bone fragility, a clinical entity we have termed O2HE (Osteo-Oto-Hepato-enteric) syndrome. 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.

Original language	English (US)
Journal	Unknown Journal
DOIs	https://doi.org/10.1101/208942
State	Published - Oct 26 2017
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Immunology and Microbiology(all)
Neuroscience(all)
Pharmacology, Toxicology and Pharmaceutics(all)

Access to Document

10.1101/208942

Fingerprint Dive into the research topics of 'Osteo-Oto-Hepato-Enteric Syndrome (O2HE) is caused by loss of function mutations in UNC45A'. Together they form a unique fingerprint.

Cite this

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., ... Fabre, A. (2017). Osteo-Oto-Hepato-Enteric Syndrome (O2HE) is caused by loss of function mutations in UNC45A. Unknown Journal. https://doi.org/10.1101/208942

Esteve, Clothilde ; Francescatto, Ludmila ; Tan, Perciliz L. ; Bourchany, Aurélie ; de Leusse, Cécile ; Marinier, Evelyne ; Blanchard, Arnaud ; Bourgeois, Patrice ; Brochier-Armanet, Céline ; Bruel, Ange Line ; Delarue, Arnauld ; Duffourd, Yannis ; Ecochard-Dugelay, Emmanuelle ; Hery, Géraldine ; Huet, Frédéric ; Gauchez, Philippe ; Gonzales, Emmanuel ; Guettier-Bouttier, Catherine ; Komuta, Mina ; Lacoste, Caroline ; Maudinas, Raphaelle ; Mazodier, Karin ; Rimet, Yves ; Rivière, Jean Baptiste ; Roquelaure, Bertrand ; Sigaudy, Sabine ; Stephenne, Xavier ; Thauvin-Robinet, Christel ; Thevenon, Julien ; Sarles, Jacques ; Levy, Nicolas ; Badens, Catherine ; Goulet, Olivier ; Hugot, Jean Pierre ; Katsanis, Nicholas ; Faivre, Laurence ; Fabre, Alexandre. / Osteo-Oto-Hepato-Enteric Syndrome (O2HE) is caused by loss of function mutations in UNC45A. In: Unknown Journal. 2017.

@article{cc27746c1ae2468096b73415938d0637,

title = "Osteo-Oto-Hepato-Enteric Syndrome (O2HE) is caused by loss of function mutations in UNC45A",

abstract = "Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with hitherto unknown syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing and bone fragility, a clinical entity we have termed O2HE (Osteo-Oto-Hepato-enteric) syndrome. 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.",

author = "Clothilde Esteve and Ludmila Francescatto and Tan, {Perciliz L.} and Aur{\'e}lie Bourchany and {de Leusse}, C{\'e}cile and Evelyne Marinier and Arnaud Blanchard and Patrice Bourgeois and C{\'e}line Brochier-Armanet and Bruel, {Ange Line} and Arnauld Delarue and Yannis Duffourd and Emmanuelle Ecochard-Dugelay and G{\'e}raldine Hery and Fr{\'e}d{\'e}ric Huet and Philippe Gauchez and Emmanuel Gonzales and Catherine Guettier-Bouttier and Mina Komuta and Caroline Lacoste and Raphaelle Maudinas and Karin Mazodier and Yves Rimet and Rivi{\`e}re, {Jean Baptiste} and Bertrand Roquelaure and Sabine Sigaudy and Xavier Stephenne and Christel Thauvin-Robinet and Julien Thevenon and Jacques Sarles and Nicolas Levy and Catherine Badens and Olivier Goulet and Hugot, {Jean Pierre} and Nicholas Katsanis and Laurence Faivre and Alexandre Fabre",

note = "Publisher Copyright: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2017",

month = oct,

day = "26",

doi = "10.1101/208942",

language = "English (US)",

journal = "Free Radical Biology and Medicine",

issn = "0891-5849",

publisher = "Elsevier Inc.",

}

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 2017, 'Osteo-Oto-Hepato-Enteric Syndrome (O2HE) is caused by loss of function mutations in UNC45A', Unknown Journal. https://doi.org/10.1101/208942

Osteo-Oto-Hepato-Enteric Syndrome (O2HE) is caused by loss of function mutations in UNC45A. / Esteve, Clothilde; Francescatto, Ludmila; Tan, Perciliz L.; Bourchany, Aurélie; de Leusse, Cécile; Marinier, Evelyne; Blanchard, Arnaud; Bourgeois, Patrice; Brochier-Armanet, Céline; Bruel, Ange Line; Delarue, Arnauld; Duffourd, Yannis; Ecochard-Dugelay, Emmanuelle; Hery, Géraldine; Huet, Frédéric; Gauchez, Philippe; Gonzales, Emmanuel; Guettier-Bouttier, Catherine; Komuta, Mina; Lacoste, Caroline; Maudinas, Raphaelle; Mazodier, Karin; Rimet, Yves; Rivière, Jean Baptiste; Roquelaure, Bertrand; Sigaudy, Sabine; Stephenne, Xavier; Thauvin-Robinet, Christel; Thevenon, Julien; Sarles, Jacques; Levy, Nicolas; Badens, Catherine; Goulet, Olivier; Hugot, Jean Pierre; Katsanis, Nicholas; Faivre, Laurence; Fabre, Alexandre.

In: Unknown Journal, 26.10.2017.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Osteo-Oto-Hepato-Enteric Syndrome (O2HE) is caused by loss of function mutations in UNC45A

AU - Esteve, Clothilde

AU - Francescatto, Ludmila

AU - Tan, Perciliz L.

AU - Bourchany, Aurélie

AU - de Leusse, Cécile

AU - Marinier, Evelyne

AU - Blanchard, Arnaud

AU - Bourgeois, Patrice

AU - Brochier-Armanet, Céline

AU - Bruel, Ange Line

AU - Delarue, Arnauld

AU - Duffourd, Yannis

AU - Ecochard-Dugelay, Emmanuelle

AU - Hery, Géraldine

AU - Huet, Frédéric

AU - Gauchez, Philippe

AU - Gonzales, Emmanuel

AU - Guettier-Bouttier, Catherine

AU - Komuta, Mina

AU - Lacoste, Caroline

AU - Maudinas, Raphaelle

AU - Mazodier, Karin

AU - Rimet, Yves

AU - Rivière, Jean Baptiste

AU - Roquelaure, Bertrand

AU - Sigaudy, Sabine

AU - Stephenne, Xavier

AU - Thauvin-Robinet, Christel

AU - Thevenon, Julien

AU - Sarles, Jacques

AU - Levy, Nicolas

AU - Badens, Catherine

AU - Goulet, Olivier

AU - Hugot, Jean Pierre

AU - Katsanis, Nicholas

AU - Faivre, Laurence

AU - Fabre, Alexandre

N1 - Publisher Copyright: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2017/10/26

Y1 - 2017/10/26

N2 - Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with hitherto unknown syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing and bone fragility, a clinical entity we have termed O2HE (Osteo-Oto-Hepato-enteric) syndrome. 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.

AB - Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with hitherto unknown syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing and bone fragility, a clinical entity we have termed O2HE (Osteo-Oto-Hepato-enteric) syndrome. 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.

UR - http://www.scopus.com/inward/record.url?scp=85095654813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85095654813&partnerID=8YFLogxK

U2 - 10.1101/208942

DO - 10.1101/208942

M3 - Article

AN - SCOPUS:85095654813

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

ER -