British and American researchers have identified new ‘candidate’ genes which they say could be responsible for congenital hearing loss.
A candidate gene is one suspected to be involved in a condition, disease or trait, based on previous knowledge or evidence. While not proven to be causative, it is a strong suspect due to its location in a region linked to the condition, its known function, or its protein product suggesting a role in mechanism.
Research shows congenital deafness (hearing loss from birth) is common, impacting about one in 1,000 babies. It is mainly caused by mutations in genes but many remain undiscovered. Researchers say understanding the exact mutations that cause deafness could hold the key to devising treatments.
Professor Andrea Streit, expert in developmental neurobiology at King’s College London, said: “Human genetics approaches have identified hundreds of ‘deafness loci’ – regions on chromosomes associated with deafness.
“These regions contain many genes, and the challenge is to identify the gene that causes deafness when mutated.”
Findings from the study, led by King’s College London in collaboration with George Washington University, were published in Development on 11 April 2025. The researchers discovered new candidates for these ‘deafness genes’.
Previous research had identified mutations in a protein, Six1, causing hearing loss so the team focused its investigation on the genes regulated by this protein.
The researchers used computer-based methods to predict more than 150 potential Six1 targets in ear progenitor cells – cells which form the entire inner ear – from chick embryos.
They selected four for further investigation and found Six1 binds to DNA regions that regulate their expression. Reducing levels of Six1 stopped these genes from being activated.
Priority candidates for causing deafness
The team then showed that most of the genes found in the chick are also expressed in human ear progenitors, and one-quarter fall into the chromosome regions associated with deafness.
“It was very exciting to find that some of the genes regulated by Six1 are located in regions of deafness loci.” Prof Streit said. “This makes them priority candidates for being causative genes of congenital hearing loss.”
The scientists also found some of the DNA regions that control Six1 target gene expression are conserved in birds and humans. They said this suggested that despite 600 million years of evolution, Six1 and its molecular mechanisms were similar in birds and humans and may control fundamental biological processes in ear development.
“It is unusual that regulatory sections of DNA, like the ones we studied, are highly conserved across species,” Prof Streit said. “The fact that we find them to be very similar from birds to humans indicates their critical role.”
The team believe further research into Six1 and the genes it regulates could provide insight into the molecular mechanisms that control how the ear normally develops.
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