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. 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 HAS1 gene. Herein, we sought to evaluate the relationship of HAS1 to the auditory system. Confirmatory Sanger sequencing used 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 mouse samples for verifying HAS1 expression. HAS1 was detected in E10.5 oticcyst. In the pup, it was localized to 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 mouse showed threshold elevations at 6, 12, and 18 kHz in the male young adult. These results reveal that HAS1 plays an important role in the auditory function. Further investigation is needed to reveal the precise mechanism of HAS1 in the auditory system. HAS1 is a candidate gene for future hereditary hearing loss genetic testing.

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. 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 _HAS1_ gene. Herein, we sought to evaluate the relationship of HAS1 to the auditory system. Confirmatory Sanger sequencing used 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 mouse samples for verifying HAS1 expression. HAS1 was detected in E10.5 oticcyst. In the pup, it was localized to 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 mouse showed threshold elevations at 6, 12, and 18 kHz in the male young adult. These results reveal that HAS1 plays an important role in the auditory function. Further investigation is needed to reveal the precise mechanism of HAS1 in the auditory system. _HAS1_ is a candidate gene for future hereditary hearing loss genetic testing.

Hyaluronan synthase 1: A novel candidate gene associated with late-onset non-syndromic hereditary hearing loss

It is with great pleasure and enthusiasm, that on behalf of the Cochlear Implant centers of the Radboud UMC in Nijmegen and Erasmus MC Sophia Children’s Hospital in Rotterdam to invite you to attend the 16th European Symposium on Pediatric Cochlear Implantation to Rotterdam, the Netherlands in 2023.

Yours sincerely, on behalf of the CI Centers at Radboud UMC and Erasmus MC,