A rare haplotype of the GJD3 gene segregating in familial Meniere's disease interferes with connexin assembly.

ABSTRACT:

Background

Familial Meniere's disease (FMD) is a rare polygenic disorder of the inner ear. Mutations in the connexin gene family, which encodes gap junction proteins, can also cause hearing loss, but their role in FMD is largely unknown.

Methods

We retrieved exome sequencing data from 94 individuals in 70 Meniere's disease (MD) families. Through gene burden analysis, we calculated the enrichment of rare variants (allele frequency < 0.05) in connexins genes in FMD individuals compared with the reference population. The connexin monomer and the homomeric connexon structural models were predicted using AlphaFold2 and HDOCK. RT-qPCR and immunofluorescence were done in mice cochleae to identify expression of the mouse ortholog candidate gene Gjd3.

Results

We found an enric

SUBMITTER: Escalera-Balsera A 

PROVIDER: S-EPMC11737067 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature