Eye movement disorder gene identified

Issue date: 11.08.08

An international team of researchers including Professor Sarah Guthrie's research group from the MRC Centre for Developmental Neurobiology at King’s College London, have identified and investigated the function of a gene mutated in the eye movement disorder, Duane Syndrome.

The collaboration was co-ordinated by Professor Elizabeth Engle at Boston Children's Hospital, USA, and included Sarah Guthrie, Professor of Developmental Neurobiology at King’s, and Drs John Chilton and Nick Gutowski at Peninsula Medical School.

The human congenital disorder Duane Syndrome affects 1 in 1,000 individuals, and results in limited horizontal (sideways) eye movements. In particular sufferers cannot move the eyeball outwards (towards the ear), whereas attempts to move the eye towards the nose result in retraction of the eyeball and closing of the eyelids. Previous neuroimaging studies showed that Duane patients have miswiring defects of the cranial nerves which control the eye muscles. Linkage analysis had also identified a region on chromosome 2 which contained the Duane genetic mutation, but the actual identity of the gene was unknown.

In the study genetic linkage studies and analysis o

f DNA from individuals in a large number of affected families world-wide was carried out by clinical teams. This led to the identification of several mutations in the racGAP signalling molecule α2-chimaerin.

Experiments then showed that the identified mutations lead to over-activation of the chimaerin molecule. This implies that neuronal signalling pathways such as those involved in nerve growth and guidance might be abnormally regulated and would as a result affect eye movement.

King’s College London