Searching for New Genes That Cause Usher Syndrome
Abstract
PURPOSE: The purpose of this project was to identify novel Usher syndrome (USH) candidate genes from phenotyping data of 9139 knockout (KO) mouse lines. METHODS: We evaluated phenotype data for concurrent retinopathy and hearing abnormalities in single-gene KO mice generated by the International Mouse Phenotyping Consortium (IMPC). A search was performed to determine whether each gene had been previously associated with retinopathy and/or deafness in humans. Bioinformatic tools were used to predict protein interactions, molecular functions, signaling pathways, and the expression of human orthologues of candidate genes in the retina and inner ear. RESULTS: We identified 18 single-gene KO lines exhibiting hearing abnormality and retinopathy after ear and eye examinations, respectively, and/or by histopathology. The molecular functions and signaling pathways of the human orthologues of the 18 candidate genes partially overlapped with those of USH genes. Particularly, FER and DYRK1B proteins were predicted to interact with proteins encoded by known ciliopathy genes. ADIPOR1, ATP8B1, and MPDZ were associated with retinal degeneration in humans. CHSY1 and IDUA may be pathogenic causes of hearing impairment in people. Furthermore, CHSY1, CSTB, and SPRED1 were located adjacent to unsolved genetic loci related to USH. CONCLUSIONS: A screen of 9139 KO mouse lines revealed 18 candidate genes exhibiting both retinal and inner ear abnormalities consistent with the principal clinical features associated with USH. As the observed phenotypes are attributed to gene deletion in mice, these genes warrant further study to determine the causation of retinal degeneration and hearing loss in patients.
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BibTeX
@article{moshiri2026searching,
title = {{Searching for New Genes That Cause Usher Syndrome}},
author = {Ala Moshiri and Niusha Kasiri and Michael Shea and Layla Ali and Benjamin Yang and Andy Shao and Dave Clary and Ann Flenniken and Mohammad Eskandarian and Oana Amarie and Lore Becker and Riccardo Sangermano and Emily Place and Kinga Bujakowska and Rachel Huckfeldt and Zorana Berberovic and Raphaël Bour and Fabrice Riet and Steve Brown and Abigail D’souza and Helmut Fuchs and Valerie Gailus-Durner and Alain Guimond and Yann Hérault and Martin Hrabě De Angelis and Aline Lux and Christophe Mittelhaeuser and Lauryl M.J. Nutter and Marcela Palkova and Jiri Lindovsky and Benoit Petit-Demouliere and Jan Prochazka and Vivian Bradaschia and Lois Kelsey and Colin Mckerlie and Miles Joseph Raishbrook and Radislav Sedlacek and Louise Lanoue and K.C. Kent Lloyd and Michel Roux and Olivia Bermingham-Mcdonogh},
journal = {American Journal of Ophthalmology},
year = {2026},
month = oct,
doi = {10.1016/j.ajo.2026.06.016},
url = {https://hal.science/hal-05786204v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Searching for New Genes That Cause Usher Syndrome
AU - Ala Moshiri
AU - Niusha Kasiri
AU - Michael Shea
AU - Layla Ali
AU - Benjamin Yang
AU - Andy Shao
AU - Dave Clary
AU - Ann Flenniken
AU - Mohammad Eskandarian
AU - Oana Amarie
AU - Lore Becker
AU - Riccardo Sangermano
AU - Emily Place
AU - Kinga Bujakowska
AU - Rachel Huckfeldt
AU - Zorana Berberovic
AU - Raphaël Bour
AU - Fabrice Riet
AU - Steve Brown
AU - Abigail D’souza
AU - Helmut Fuchs
AU - Valerie Gailus-Durner
AU - Alain Guimond
AU - Yann Hérault
AU - Martin Hrabě De Angelis
AU - Aline Lux
AU - Christophe Mittelhaeuser
AU - Lauryl M.J. Nutter
AU - Marcela Palkova
AU - Jiri Lindovsky
AU - Benoit Petit-Demouliere
AU - Jan Prochazka
AU - Vivian Bradaschia
AU - Lois Kelsey
AU - Colin Mckerlie
AU - Miles Joseph Raishbrook
AU - Radislav Sedlacek
AU - Louise Lanoue
AU - K.C. Kent Lloyd
AU - Michel Roux
AU - Olivia Bermingham-Mcdonogh
PY - 2026
DA - 2026/10/08
JO - American Journal of Ophthalmology
DO - 10.1016/j.ajo.2026.06.016
UR - https://hal.science/hal-05786204v1
AB - PURPOSE: The purpose of this project was to identify novel Usher syndrome (USH) candidate genes from phenotyping data of 9139 knockout (KO) mouse lines. METHODS: We evaluated phenotype data for concurrent retinopathy and hearing abnormalities in single-gene KO mice generated by the International Mouse Phenotyping Consortium (IMPC). A search was performed to determine whether each gene had been previously associated with retinopathy and/or deafness in humans. Bioinformatic tools were used to predict protein interactions, molecular functions, signaling pathways, and the expression of human orthologues of candidate genes in the retina and inner ear. RESULTS: We identified 18 single-gene KO lines exhibiting hearing abnormality and retinopathy after ear and eye examinations, respectively, and/or by histopathology. The molecular functions and signaling pathways of the human orthologues of the 18 candidate genes partially overlapped with those of USH genes. Particularly, FER and DYRK1B proteins were predicted to interact with proteins encoded by known ciliopathy genes. ADIPOR1, ATP8B1, and MPDZ were associated with retinal degeneration in humans. CHSY1 and IDUA may be pathogenic causes of hearing impairment in people. Furthermore, CHSY1, CSTB, and SPRED1 were located adjacent to unsolved genetic loci related to USH. CONCLUSIONS: A screen of 9139 KO mouse lines revealed 18 candidate genes exhibiting both retinal and inner ear abnormalities consistent with the principal clinical features associated with USH. As the observed phenotypes are attributed to gene deletion in mice, these genes warrant further study to determine the causation of retinal degeneration and hearing loss in patients.
SN - 0002-9394
ER -