Abstract
Usher syndrome (USH) is an autosomal recessive disorder characterized by sensorineural hearing loss, progressive pigmentary retinopathy, and vestibular dysfunction. The degree and onset of hearing loss vary among subtypes I, II, and III, while blindness often occurs in the second to fourth decades of life. Usher type III (USH3), characterized by postlingual progressive sensorineural hearing loss, varying levels of vestibular dysfunction, and varying degrees of visual impairment, typically manifests in the first to second decades of life. While USH3 is rare, it is highly prevalent in certain populations. RP61, USH3, and USH3A symbolize the same disorder, with the latter symbol used more frequently in recent literature. This review focuses on the clinical features, epidemiology, molecular genetics, treatment, and research advances for sensory deficits in USH3A.
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adapted from Mammano et al. (2007), panel C’’ reprinted from Geng et al (2017), panels D and E reprinted from Neurosciences: Exploring the Brain (Bear et al. 2007), and panel F reprinted from Physiology and Pathology of Chloride Transporters and Channels in the Nervous System (Alvarez-Leefmans and Delpire 2009) with permission
modified from Tian et al. (2009) under Creative Common license BY-NC-SA 4.0 and panel D modified from Lukacs et al. (2016) with permission
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Abbreviations
- CLRN1:
-
The clarin-1 protein in mice or human
- CLRN1 :
-
Human clarin-1 gene
- Clrn1 :
-
Mice clarin-1 gene
- USH3A :
-
Former designation for the gene associated with USHIII/IIIA locus; replaced by the clarin-1 gene.
- USH3A:
-
Associated with pathogenic variants in CLRN1
- IHCs:
-
Inner hair cells
- OHCs:
-
Outer hair cells
- USH:
-
Usher syndrome
- USH1:
-
Usher type I
- USH2:
-
Usher type II
- USH3:
-
Usher type III
- ENG:
-
Electronystagmography
- VNG:
-
Videonystagmography
- RP:
-
Retinitis Pigmentosa
- ERG:
-
Electroretinogram
- UTRs:
-
Untranslated regions
- MET:
-
Mechanoelectrical transduction
- INL:
-
Inner nuclear layer
- CI:
-
Cochlear implantation
- P:
-
Postnatal
- PTA:
-
Pure tone average
- PHL:
-
Progressive hearing loss
- iPSCs:
-
Induced pluripotent stem cells
- MSCs:
-
Mesenchymal stem cells
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Acknowledgements
The authors acknowledge the support of Usher III Initiative, Chicago, which played a pioneering role in bringing together a team of scientists and experts around the world to develop therapies to treat both vision and hearing loss in individuals diagnosed with USH3A. Basic science research related clarin-1 in KNA’s lab was supported by the National Institutes of Health Grants (R01-DC010816) and the Maniglia Endowed Chair, University Hospitals Cleveland Medical Center.
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Marouf, A., Johnson, B. & Alagramam, K.N. Usher syndrome IIIA: a review of the disorder and preclinical research advances in therapeutic approaches. Hum Genet 141, 759–783 (2022). https://doi.org/10.1007/s00439-022-02446-9
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DOI: https://doi.org/10.1007/s00439-022-02446-9