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KMID : 1195620220150030220
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Clinical and Experimental Otorhinolaryngology
2022 Volume.15 No. 3 p.220 ~ p.229
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Hyaluronan Synthase 1: A Novel Candidate Gene Associated With Late-Onset Non-syndromic Hereditary Hearing Loss
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Umugire Alphonse
Lee Sung-Su
Lee Chang-Joon
Choi Young-Mi
Kim Tae-Kyoung
Cho Hyong-Ho
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Abstract
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Objectives: Hyaluronan synthase 1 (HAS1) is a membrane-bound protein that is abundant in the epidermis and dermis, and it is important for skin function. However, its association with hearing loss has not yet been studied. Herein, we sought to evaluate the potential contribution of HAS1: c.1082G>A to genetic hearing loss.
Methods: We used whole-exome sequencing to analyze blood DNA samples of six patients of a family with autosomal dominant familial late-onset progressive hearing loss, which was revealed to be related to a variant of the HAS1 gene. Confirmatory Sanger sequencing was performed with samples from 10 members. A missense variant was detected in HAS1 (c.1082 G>A, p.Cys361Tyr). In silico analyses predicted this variant to result in the functional loss of HAS1. Immunostaining was conducted using wild-type mouse samples to verify HAS1 expression.
Results: Has1 was detected in an otocyst at E10.5. In the pup, Has1 expression was localized in the stria vascularis (SV), hair cells, supporting cells of the organ of Corti, and some spiral ganglion neurons. SV marginal cells markedly expressed Has1 in the adult stage. The hearing threshold in the Has1-depleted condition was investigated by accessing the International Mouse Phenotyping Consortium’s Auditory Brainstem Response (ABR) data. ABR of Has1 knock-out mice showed threshold elevations at 6, 12, and 18 kHz in young male adults.
Conclusion: HAS1 may have a close relationship with auditory function and genetic hearing loss. Further investigation is needed to reveal the precise role of HAS1 in the auditory system. HAS1 is a candidate gene for future hereditary hearing loss genetic testing.
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KEYWORD
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Hyaluronan Synthases, Mutation, Missense, Whole Exome Sequencing, Nonsyndromic Sensorineural Hearing Loss
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