A study has identified 211 distinct mutations in 49 genes associated with deafness including more than one-third that are newly detected.
The researchers from France, North Africa and the Middle East said they had uncovered the genetic basis of deafness occurring before the onset of language. They reported their findings in PNAS on 8 December 2025.
They said deafness occurred at all stages of life. The most common form – sensorineural hearing loss – occurred independently or as part of syndromes associated with other symptoms such as Usher Syndrome type 1.
The researchers were from the reConnect Institute, a foundation hosted by the Institut Pasteur at the Hearing Institute (Institut Pasteur/Inserm/CNRS) in France, the Pasteur Institute of Tunis, Institut Pasteur du Maroc, and universities and hospitals in Algeria, Morrocco, Mauritania, and Jordan.
They uncovered the genetic basis of congenital deafness in 450 unrelated patients by analysing genetic data from patients in Algeria, Morrocco, Mauritania, and Jordan.
“By sequencing the genomic regions known to contain genes responsible for deafness, we identified 211 distinct mutations in 49 genes, 36% of which were new,” said senior author, Dr Crystel Bonnet.
“While 154 genes are known to be responsible for isolated deafness, mutations in about ten of them alone account for approximately three-quarters of deafness cases in each country.
“Although the genes involved in isolated deafness are similar across the four countries studied, their mutations are, in most cases, family-specific, with the exception of a few particularly frequent mutations affecting the GJB2 gene.”
Dr Bonnet is a research engineer in the Hearing Therapy Innovation Laboratory, reConnect Institute at the Hearing Institute, France.
Distinguishing between types
The researchers said a recurring challenge in diagnosing deafness was that certain genes, depending on the mutations they carry, were responsible for either isolated deafness or Usher syndrome type 1. Until now, no molecular characteristics had been identified that could distinguish between these two types of mutations.
“We hypothesised that these difficulties could stem from incomplete or inaccurate classification of some of these mutations,” said geneticist Dr Christine Petit, head of the Hearing Therapy Innovation Laboratory at the reConnect Institute.
“Our analyses show that this is indeed the case. Certain mutations, when present in a homozygous state in these genes, lead to isolated deafness.
“However, we have observed that they can have a deleterious effect on vision. This effect can be unmasked when this mutation is associated with another mutation that inactivates the other copy of the gene.”
The researchers said the reclassification of mutations should improve the quality of genetic counselling provided to families around the world by providing guidance on the most appropriate communication method for each child, such as cochlear implantation or sign language. It should also support regular ophthalmological follow-up.
