Researchers link microRNA gene to hearing loss
14 April 2009
Researchers from the UK and Spain have identified a mutation in a gene for a microRNA that is associated with progressive hearing loss. MicroRNAs, which are short lengths of RNA, are thought to be able alter the expression of hundreds of genes.
To date, the genes implicated in deafness contain the genetic information needed to make proteins. The gene identified in this research, miR-96, is the first microRNA gene to be associated with hearing loss or with any inherited disorder. This is also the first time researchers have found a disease-causing mutation in the mature sequence of a microRNA.
Scientists led by Professor Karen Steel at the Wellcome Trust Sanger Institute studied a new line of mice called ‘diminuendo’, which show progressive hearing loss from an early age. In a parallel study, a team from the Hospital Ramón y Cajal, Madrid, Spain examined people with a family history of deafness.
Both teams narrowed down the mutation causing the hearing loss to a gene called miR-96, which is found, in humans, on chromosome 7. This gene contains the information needed to produce a microRNA.
The researchers at the Sanger Institute showed that the mutant form of the gene disrupted the development of sensory hair cells in the ears of the mice. Such cells are vital for hearing as they detect the vibrations of sound and convert them into electrical signals that trigger activity in the auditory nerves.
Mice with two copies of the mutant gene were born with malformed hair cells that degenerated from an early age. In mice with one copy of the mutant gene, the effects were less severe, but also became worse with age.
The researchers found that the mutation in the microRNA gene altered the expression of hundreds of different mRNAs. They are now studying five genes whose mRNA expression was affected by the mutant microRNA, to see if they are involved in causing the damage to the hair cells.
It is hoped that this kind of work will ultimately help researchers develop of therapies to prevent or limit the effects of progressive hearing loss, a distressing condition that affects the majority of people aged over 70.
These studies were part-funded by the Wellcome Trust. For more on Professor Steel’s work see Sound science: Exploring the genetics of hearing loss (feature: 14 April 2009) .
Image: A child's ear; Fiona Pragoff, Wellcome Images
References
- Mencía A et al. Mutations in the seed region of human miR-96 are responsible for non-syndromic progressive hearing loss. Nat Genet 12 April 2009 [Epub ahead of print].
- Lewis M et al. An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice. Nat Genet 12 April 2009 [Epub ahead of print].