Hyaluronan Synthase 1: A Novel Candidate Gene Associated With Late-Onset Non-syndromic Hereditary Hearing Loss

Abstract

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 <i>HAS1</i>: 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 <i>HAS1</i> gene. Confirmatory Sanger sequencing was performed with samples from 10 members. A missense variant was detected in <i>HAS1</i> (c.1082 G>A, p.Cys361Tyr). <i>In silico</i> 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 <i>Has1</i> 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. <i>HAS1</i> is a candidate gene for future hereditary hearing loss genetic testing.