New genetic hearing discovery gives hope to millions

7 November 2008

New research, published in the current edition of in PLoS Genetics has defined a mutation in the mouse genome that closely mimics progressive hearing loss in humans. The mutation disrupts the function of the sensory cells (hair cells) in the inner ear, beginning even before the cells show any signs of physical damage. Professor Karen Steel from the Wellcome Trust Sanger Institute led the study which is partially supported by Deafness Research UK.

Hearing deficits become more common in humans from birth onwards, with rates doubling from birth to age ten. A wide range of factors means that progressive loss of hearing affects more than half of people over the age of 50. Physical damage to the ear, exposure to excessive noise levels, ototoxic drugs, and infections can all lead to hearing loss and genetic influences can also play a major role. The new research shows that a mutation called Oblivion affects a pump in the hair cell membrane which normally transports molecules of calcium across the membrane from the inside to the outside of the cell.

"When we mapped the mutation to the mouse genome, we quickly found a probable cause for hearing loss," explains Professor Steel. "We showed that the mutant mice carried a change in one letter of their genetic code in a gene called Atp2b2. Changing a specific C to a T in this gene stops it from producing a normal molecular pump that is needed to keep hair cells in the ear working efficiently by pumping excess calcium out of the cell.

Vivienne Michael, Chief Executive of Deafness Research UK, said: “Remarkably, although we know of many genes involved in childhood deafness, their role in progressive hearing loss is poorly understood.

We are hopeful that this latest research could open the door to understanding, preventing and eventually curing progressive hearing loss altogether. We need more funding to ensure that excellent research like this, which could ultimately improve the lives of millions, continues and develops.”

"This is part of a systematic approach to identifying genes that play a role in hearing and deafness," says Professor Steel. "We know of only a handful of gene variants involved in progressive hearing loss, identified over the past 15 years. We need a better approach to understanding hearing loss: this is one of the first fruits of that programme."

In the new research, the team worked with colleagues in Munich and Padua to study the biology of the hearing responses and the structure of the cells in the ear.

Mice were systematically examined for an impaired hearing response. One mouse mutation, Oblivion, showed some features in common with forms of human deafness. If both copies of the Oblivion gene were mutant, the mice were completely deaf from birth. However, if a non-mutant form was inherited from one parent and a mutant form from the other, the mice show progressive hearing loss during the first three months of life.

"If one copy of the gene is affected, the pump works, but not well enough and hearing gradually fails,” adds Professor Steel. “If both copies are affected, the pump hardly works at all and hearing is lost before birth."

Although other mutations have been described, Oblivion is unique in the way it leads to hearing loss due to mutations in Atp2b2. The deficits in hearing are seen before any physical sign can be seen of damage to the hair cell. The effect mimics human progressive loss of hearing. Indeed, some instances of human hearing loss are due, at least in part, to mutation in the human Atp2b2 gene.

"One aim of identifying and characterising mice with impaired hearing is to help us to understand the biology of this remarkable sense," says Professor Steel. "Improving our understanding of the molecular and cellular action of genetic variants will help us to develop improved diagnostics and improved treatments for humans."

 

For further information on deafness and deafness-related conditions, call freephone 0808 808 2222 or visit Deafness Research UK’s website at www.deafnessresearch.org.uk

About Deafness Research UK

• Deafness Research UK is the country’s only charity dedicated to finding new cures, treatments and technologies for deaf, hard of hearing and other hearing impaired people.
• The charity supports high quality medical research into the prevention, diagnosis and treatment of all forms of hearing impairment including tinnitus.
• The Deafness Research UK Information Service provides free information and advice based on the latest scientific evidence and informed by leading experts. The Information Service can be contacted on Freephone 0808 808 2222
• For more information on research into deafness, tinnitus and other hearing conditions, log on to the website at www.deafnessresearch.org.uk where you can access a wide range of information. Alternatively you can e-mail Deafness Research UK at info@deafnessresearch.org.uk
• One in seven people in the UK – almost nine million people - suffer hearing loss.
• Deafness Research UK was founded in 1985 by Lord (Jack) and Lady Ashley of Stoke.
• In January 2008, Action for Tinnitus Research (ATR) was linked with Deafness Research UK under a uniting direction order under Section 96 (6) of the Charities Act 1993.

Press enquiries

Jon Gardner, BeyondPR. Direct line 0114 275 6996. Mobile 07930 697773. email: jon.gardner@beyondpr.co.uk

Ref: DRUK0098 – Genetic discovery