Searching for New Genes That Cause Usher Syndrome.

Ala Moshiri; Niusha Kasiri; Michael Shea; Layla Ali; Benjamin Yang; Andy Shao; Dave Clary; Ann M Flenniken; Mohammad Eskandarian; Oana V Amarie; Lore Becker; Riccardo Sangermano; Emily M Place; Kinga M Bujakowska; Rachel M Huckfeldt; Zorana Berberovic; Rapha&#xeb;l Bour; Fabrice Riet; Steve D Brown; Abigail D'Souza; Helmut Fuchs; Valerie Gailus-Durner; Alain Guimond; Yann H&#xe9;rault; Martin Hrab&#x11b; DE Angelis; Aline Lux; Christophe Mittelhaeuser; Lauryl M J Nutter; Marcela Palkova; Jiri Lindovsky; Benoit Petit-Demouliere; Jan Prochazka; Vivian Bradaschia; Lois Kelsey; Colin McKerlie; Miles Joseph Raishbrook; Radislav Sedlacek; INTERNATIONAL MOUSE PHENOTYPING CONSORTIUM; Louise Lanoue; K C Kent Lloyd; Michel J Roux; Olivia Bermingham-McDonogh

doi:10.1016/j.ajo.2026.06.016

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Searching for New Genes That Cause Usher Syndrome.

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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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Animals Usher Syndromes Mice Mice, Knockout Humans Phenotype Disease Models, Animal Journal Article

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Ala Moshiri, Niusha Kasiri, Michael Shea, Layla Ali, Benjamin Yang, Andy Shao, Dave Clary, Ann M Flenniken, Mohammad Eskandarian, Oana V Amarie, Lore Becker, Riccardo Sangermano, Emily M Place, Kinga M Bujakowska, Rachel M Huckfeldt, Zorana Berberovic, Raphaël Bour, Fabrice Riet, Steve D Brown, Abigail D'Souza, Helmut Fuchs, Valerie Gailus-Durner, Alain Guimond, Yann Hérault, Martin Hrabě DE Angelis, Aline Lux, Christophe Mittelhaeuser, Lauryl M J Nutter, Marcela Palkova, Jiri Lindovsky, Benoit Petit-Demouliere, Jan Prochazka, Vivian Bradaschia, Lois Kelsey, Colin McKerlie, Miles Joseph Raishbrook, Radislav Sedlacek, INTERNATIONAL MOUSE PHENOTYPING CONSORTIUM, Louise Lanoue, K C Kent Lloyd, Michel J Roux, Olivia Bermingham-McDonogh. 2026-06-18. Searching for New Genes That Cause Usher Syndrome.. https://doi.org/10.1016/j.ajo.2026.06.016

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