A new research discovery could help more families affected by a rare inherited condition, Perrault Syndrome, get answers about the cause of their hearing loss.
Researchers at Manchester University NHS Foundation Trust (MFT) have identified changes in a gene called ‘GPN2’ that can cause Perrault syndrome — a rare condition linked to severe hearing loss and, in women, ovarian failure.
The discovery, partly supported by RNID-funded research, adds to growing knowledge of the genetic causes of hearing loss and could help improve diagnosis for families in the future.
What is Perrault Syndrome?
Perrault syndrome is a rare inherited condition and affected individuals have severe to profound bilateral hearing loss (hearing loss in both ears). This hearing loss can be present at birth or develop and worsen during childhood.
Affected women also have ovarian failure that results in infertility. As ovarian problems are a key feature of the diagnosis, men are rarely diagnosed, even though they have the same risk of being affected. Early diagnosis in children is difficult but is improving due to increased genetic testing in children with hearing loss. Early, accurate diagnosis can result in improved hearing outcomes.
Over the past ten years different research groups have identified several genes that, when altered, can result in Perrault syndrome. Yet, for many families the genetic diagnosis is still uncertain.
The genetic discovery
In 2021 Thomas Smith was awarded a RNID PhD studentship funded by the The Freemasons’ Charity to work on the genetic causes of a rare inherited condition called Perrault syndrome.
In 2025, with colleagues at The University of Manchester (UoM) and colleagues across the UK and worldwide, his studies led to the identification of two genes called ‘DAP3’ and ‘MRPL49’, which caused Perrault syndrome in 14 families. Like other genes that cause Perrault syndrome DAP3 and MRPL49 alter the mitochondria – the energy bundles in cells in the body.
Now in 2026, Tom has discovered that genetic changes in a different gene, GPN2, can also cause Perrault syndrome. The finding was made through the studies of three families from Pakistan, Ireland and Australia. Interestingly, GPN2 has no role in the mitochondria and indicates that different pathways can lead to hearing loss.
The study*, which is published in the leading journal the American Journal of Human Genetics, will be the first step in developing effective novel treatments.
Dr Smith who has been awarded his doctorate said:
The award from RNID allowed me to learn lots of new techniques in the laboratory to discover these new causes of hearing loss. I am continuing to work in hearing health by researching schwannomatosis, a rare tumour-predisposition condition which can, in some cases, affect the hearing nerve.”
The future
This discovery adds an important piece to the puzzle of Perrault syndrome and will help improve understanding of the genetic causes of rare forms of hearing loss. By identifying more genes linked to the condition, researchers can support faster, more accurate diagnosis for families and build the evidence needed to develop future treatments.
Continued investment in hearing research is vital to make discoveries like this possible and to bring new hope to people affected by rare inherited hearing conditions.
Ralph Holme, Director of Research at RNID, added:
This research is an incredibly exciting breakthrough, and represents a major step forwards in our understanding of Perrault syndrome. The identification of a new gene associated with hearing loss not only means more people can now get an accurate diagnosis of the cause of their hearing loss, but it also provides vital insights that could pave the way for treatments for Perrault syndrome and other more common forms of hearing loss in the future.
We are delighted to co-fund vital research like this to help to improve understanding of hearing loss and bring us closer to more effective treatments.”
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* This work was supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre (BRC): Manchester, RNID with support from The Freemasons’ Charity and Medical Research Council. Professor Bill Newman, Consultant in Genomic Medicine at MFT, Professor at UoM and Rare Conditions Co-Theme Lead at the NIHR BRC: Manchester, led the research.