Tuesday 18 May 2005
Damaged gene causes impaired vision and autism in NZ family
A University of Otago research team today announced a major breakthrough in understanding a severe genetic disorder that
affects a large New Zealand family.
The inherited eye condition has been in the family for at least five generations and causes vision impairment in both
males and females, but is most severe in male family members. In addition, some male children have intellectual
disability and autism.
The research has discovered a subtle alteration in a calcium channel gene that has profound effects on channel function.
This particular calcium channel is found in the light-sensing cells of the eye. It is part of a signalling pathway that
converts light stimuli into nerve messages to the brain. Normally entry of calcium via this channel is tightly regulated
but the damaged channel is hyperactive.
Molecular geneticist, Dr Marion Maw, says it is not surprising that vision is impaired in family members.
“The healthy version of this calcium channel lets calcium enter the light-sensing cells of the eye during darkness. The
damaged channel is hyperactive and probably lets calcium enter the cells regardless of whether it is dark or light.
“Other forms of damage to this same gene cause a clinically related form of visual impairment called X-linked incomplete
congenital stationary night blindness,” she says.
The association of abnormal calcium channel activity with intellectual impairment and autism intrigues the researchers.
“We wondered if the association was a coincidence, but a recent study suggests otherwise. Researchers in New York have
shown that Timothy syndrome, a multi-system disorder including autism and intellectual impairment, is caused by damage
to a different calcium channel gene. Moreover the damaged channel again permits excess calcium to enter cells,” Dr Maw
says.
The project has been running since 1998, but the work is by no means complete.
“We still need to find out precisely how the damaged channel causes each of the clinical symptoms. Pharmacological
agents already exist that are known to block the activity of calcium channels. We want to investigate whether such
agents could be used to develop a treatment for this rare disorder,” she says.
The project has been carried out in collaboration with Auckland ophthalmologists Drs Carolyn Hope, Dianne Sharp and
Gillian Clover, and in partnership with a large North Island whanau. The research team has also worked in collaboration
with Professor Steffen Hering of the Institute of Toxicology and Pharmacology in Vienna.
Ophthalmologist Dr Carolyn Hope arranged for family members to have eye examinations. The detailed clinical findings
were published in the April issue of Clinical and Experimental Ophthalmology.
Family members taking part in the study also provided blood samples for genetic analyses. Student Ariana Hemara-Wahanui
identified a subtle alteration in the calcium channel gene in 2000 during research for her MSc thesis. Dr Maw then
formed a collaboration with Prof Hering to investigate the effects of this change on calcium channel function.
Patricia Lundon-Treweek, a member of the whanau and co-author on the study, is herself affected by the disorder. Two of
her three children have inherited the condition. She played a key role in the partnership between the whanau, clinicians
and researchers.
The Health Research Council and Lottery Grants Board provided the major funding for the genetic and clinical research.
In addition, Ariana Hemara-Wahanui was supported in her MSc studies by grants from several Maori trust boards, the
University of Otago, and the Ministry of Science, Research and Technology.
The research findings will be published this week in the prestigious international journal Proceedings of the National
Academy of Sciences.
Although the disorder is very rare, the researchers hope that future studies may provide insights of more general
importance. In particular, two of the symptoms in the present family, high myopia (short-sightedness) and autism, are
each common disorders in the general population.
ENDS