A Rare Variant in TRIOBP Linked to Occupational Noise Exposure in Meniere Disease

Abstract

Meniere disease (MD) is an inner ear disorder characterised by episodic vertigo, tinnitus, and sensorineural hearing loss. Previous sequencing studies have identified rare mutations in 16 genes expressed in hair cells, many of which are involved in maintaining the structure and stability of stereocilia. Experimental evidence supports that noise-induced hearing loss is associated with structural damage in the hair cell stereocilia. We hypothesise that rare variants in genes expressed in hair cell stereocilia may predispose individuals to MD with occupational noise exposure. To explore this, we analysed whole exome sequencing data from MD patients with documented histories of occupational noise exposure. A rare missense variant chr22:37769343C>T in the TRIOBP gene was identified in three individuals (OR=1,846 (203-8192), p=3.39x10-5). In silico protein modelling suggests this variant (p.R2273C) interacts with the Actin C chain, potentially affecting cytoskeletal integrity in hair cells. Immunolabelling confirmed TRIOBP expression in the stereocilia rootlets of cochlear and vestibular hair cells, supporting its structural function in both sensory epithelia. Furthermore, retrieved MD single-cell ATAC-seq data revealed reduced chromatin accessibility at the RFX3 transcription factor locus, suggesting a transcriptional TRIOBP downregulation. Our results support that occupational noise exposure may trigger MD in the carriers of TRIOBP mutations.