Thomas Smith is a PhD student in Professor William Newman’s lab at the University of Manchester. His studentship began in 2021. The Masonic Charitable Foundation is fully funding this studentship.
Perrault syndrome is a rare inherited condition and affected individuals have severe to profound hearing loss. 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 this research group, and others, have identified six different genes that, when altered, can result in Perrault syndrome. The changes in these genes all lead to problems with the mitochondria, tiny structures inside cells that provide the cell with energy. The cells we rely on for hearing require huge amounts of energy to work correctly, and so hearing is especially sensitive to problems with mitochondria. Recent genetic sequencing work undertaken by the research team has identified an additional five new genes linked to Perrault syndrome which are also important in the mitochondria.
- To generate further evidence that these new genes cause Perrault syndrome, and to understand how they are involved.
- To use state of the art genomic technologies to identify new genes that cause Perrault syndrome in people where no genetic cause is known.
- To develop a better understanding of Perrault syndrome that will form the basis of future treatment.
The student will analyse mitochondria in yeast cells and human cells containing the genetic changes identified in patients with Perrault syndrome, and look at the impact of these changes on how the mitochondria work. The student will also develop a way to measure the activity of the genes which contain these changes, to look at the impact of the specific change on the gene’s activity. This information will help to explain how these genetic changes lead to changes in cells that ultimately cause the hearing loss associated with Perrault syndrome.
The results of this work will to improve the diagnosis of Perrault syndrome, and improve our understanding of how problems with mitochondria can lead to hearing loss. Understanding rare types of hearing loss, such as Perrault syndrome, may also give important insights into more common forms of hearing loss, like auditory neuropathy.