Researchers identify a new form of disease gene associated with Rett syndrome

Toronto, ON – March 22, 2004 – Scientists at the Hospital for Sick Children, the Centre for Addiction and Mental Health (CAMH) and the University of Toronto (U of T) have identified an alternate form of the disease gene and protein for the neurodevelopmental condition Rett syndrome.

This discovery is being incorporated into a new molecular test that will aid not only in the diagnosis of Rett syndrome, but also for other developmental disabilities. The research is reported in the April issue of the scientific journal Nature Genetics (available online March 21, 2004).

“The previously identified gene MECP2 was only found in approximately 80% of patients with Rett syndrome,” says Dr Berge Minassian, the study’s principal investigator, a neurologist and scientist at Sick Children’s Hospital, and an assistant professor in the department of paediatrics at U of T. “Our discovery suggests that a defective alternate form of the MECP2 gene causes Rett syndrome.”

The protein produced by the new alternate gene is different than the protein that was first associated with Rett syndrome in 1999. In the current work, this novel molecule was found to be disrupted in some Rett syndrome patients while the original form of the protein remained intact. The new protein is also the predominant form in the brain, strongly indicating that it is the disease-relevant protein.

“Our group’s interest in Rett syndrome is relatively recent,” says Dr John Vincent, co-principal investigator of the study, head of the molecular neuropsychiatry & development laboratory at CAMH, and assistant professor in the department of psychiatry at U of T. “Our fresh look at this problem was less affected by established dogma, and allowed us this new insight.”

Rett syndrome is a genetic neurological disorder that occurs almost exclusively in girls, as the gene is found on the X chromosome. Babies with Rett syndrome appear to develop normally until 6 to 18 months of age. They then enter a period of regression, losing speech and other skills they had acquired. Most of the children develop seizures, repetitive hand movements, developmental delay, and motor-control problems, and they often have autistic tendencies. Rett syndrome is believed to affect 1 in 10,000 females.

“Since the Rett syndrome genetic tests are used not only to confirm a diagnosis of Rett syndrome, but also for ‘negative inclusion’ in other developmental disabilities such as cerebral palsy, forms of mental retardation and autism, we expect this new discovery to have great clinical utility,” adds Dr Minassian.

The research was enabled through the assistance of clinical collaborators Dr Carolyn Schanen at Nemours Biomedical Research, Alfred I duPont Hospital for Children in Delaware, Dr Patrick MacLeod at the University of British Columbia, and Dr Michael Friez at Greenwood Genetic Center in South Carolina. This research was supported by the Canadian Institutes of Health Research – Neuromuscular Research Partnership, the Hospital for Sick Children Foundation, and a U of T Dean’s Award to Dr Vincent.