PuSH - Publication Server of Helmholtz Zentrum München

Moshiri, A.* ; Kasiri, N.* ; Shea, M.* ; Ali, L.* ; Yang, B.* ; Shao, A.* ; Clary, D.* ; Flenniken, A.M.* ; Eskandarian, M.* ; Amarie, O.V. ; Becker, L. ; Sangermano, R.* ; Place, E.M.* ; Bujakowska, K.M.* ; Huckfeldt, R.M.* ; Berberovic, Z.* ; Bour, R.* ; Riet, F.* ; Brown, S.D.* ; D'Souza, A.* ; Fuchs, H. ; Gailus-Durner, V. ; Guimond, A.* ; Hérault, Y.* ; Hrabě de Angelis, M. ; Lux, A.* ; Mittelhauser, C.* ; Nutter, L.M.J.* ; Palkova, M.* ; Lindovsky, J.* ; Petit-Demouliere, B.* ; Prochazka, J.* ; Bradaschia, V.* ; Kelsey, L.* ; McKerlie, C.* ; Raishbrook, M.J.* ; Sedlacek, R.* ; Lanoue, L.* ; Lloyd, K.K.* ; Roux, M.J.* ; Bermingham-McDonogh, O.*

Searching for new genes that cause usher syndrome.

Am. J. Ophthalmol., DOI: 10.1016/j.ajo.2026.06.016 (2026)
Postprint Research data DOI PMC
Open Access Green
PURPOSE: The purpose of this project was to identify novel Usher syndrome (USH) candidate genes from phenotyping data of 9,139 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 if each gene had been previously established in retinopathy and/or deafness in humans. Bioinformatic tools were used to predict protein interactions, molecular functions, signaling pathways, and expression of human orthologs of candidate genes in retina and inner ear. RESULTS: We identified 18 single-gene KO lines exhibiting hearing abnormality and retinopathy after ear and eye examination, respectively, and/or by histopathology. The molecular functions and signaling pathways of the human orthologues of 18 candidate genes partially overlapped with 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 a pathogenic cause of hearing impairment in people. Additionally, CHSY1, CSTB and SPRED1 were located adjacent to unsolved genetic loci related to USH. CONCLUSIONS: A screen of 9,139 KO mouse lines revealed 18 candidate genes exhibiting both retinal and inner ear abnormality consistent with principle clinical features associated with USH. As the observed phenotypes are attributed to gene deletion in mice, these genes warrant further study to determine causation of retinal degeneration and hearing loss in patients.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Keywords Auditory Abnormality ; Dual Sensory Impairment ; Knockout Mouse ; Retinal Abnormality ; Usher Syndrome ; Genetic Variants
ISSN (print) / ISBN 0002-9394
e-ISSN 1879-1891
Journal American Journal of Ophthalmology
Publisher Elsevier
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)