Epilespy & Genetic Research
Canada
In May, researchers at the McGill University Health Centre (MUHC) in Montreal announced that they have identified a gene underlying juvenile myoclonic epilepsy.
Previously, a few mutated genes have been shown to be associated with rare forms of epilepsy. However, the variability in clinical features of more common epilepsies has hampered the search for genetic bases of these syndromes.
This collaborative study, led by Dr. Guy Rouleau (MUHC neurologist, and professor of neurology and neurosurgery at McGill University), co-authored by Patrick Cossette, and including researchers from the Université de Montréal and University of Toronto, analyzed DNA from 14 members of a French-Canadian family, 8 of whom have JME. In those 8, researchers found identical mutations in a well-characterized gene, GABRA. This gene encodes the alpha 1 subunit of the GABAA receptor (a chloride channel) which is involved in neuronal transmission.
Research confirmed that this mutation alters the function of the GABAA receptor: the mutant protein has diminished activity in cultured cells. This results in abnormal electrical patterns in the brain. There are 16 different subunits which can contribute to a functional GABAA receptor in the brain.
Previous research shows that mutations in a different subunit of the GABAA receptor are involved in fever-induced seizures. This study, in which the GABAA receptor is implicated in a distinct and more common seizure disorder, suggests that this molecule may be centrally involved in epileptic syndromes. Screening families for mutations in each subunit may yield further insight.
Most people living with epilepsy receive anti-seizure medication therapy throughout their lives, which may cause severe side effects. Identifying and characterizing the genes which cause epilepsies may help in designing more specifically targeted drugs for the treatment of these disorders.
Australia
The research team led by Josef Gecz, Department of Cytogenetics and Molecular Genetics at the Women and Children's Hospital (Adelaide, Australia) reports that it has discovered a gene linked to epilepsy and learning disabilities.
They report that the gene affects the way the brain works by controlling how, where and when other genes function. A mutation in the gene can produce a number of different conditions, including epilepsy, infantile spasms (West syndrome), dystonia (a disorder of muscle tone) and learning problems. The gene, on the x-chromosome, is one of about 100 genes on that chromosome that can affect IQ.
Genetic material for their studies came from 9 families in Australia, Belgium, Canada, and Norway.
USA
Researchers at New York's Columbia University Health Sciences Center have identified a gene implicated in auditory epilepsy, a rare form of epilepsy which produces hallucinations of sound, among other symptoms. They believe that their finding could provide insights into the cause of all types of epilepsy.
Led by Ruth Ottman, PhD, professor of epidemiology in the Mailman School of Public Health and deputy director of research at the Gertrude H. Sergievsky Center, both at Columbia University, investigators identified the LGI1 gene by extensively studying 5 families in which some members have auditory epilepsy. This gene seems to play a role in how nerve cells migrate during development, creating "faulty wiring".
During the study, Ottman and her colleagues looked at the pattern of inheritance of auditory epilepsy in the 5 families. They collected blood from 105 members of those families and studied the DNA from 85 of them. From prior studies of 1 family, they knew that a gene associated with epilepsy with auditory symptoms was on chromosome 10. During this research, the scientists identified the gene by studying the DNA from the first family and 4 other families: they found mutations in the affected individuals. They also found that 70% of individuals with mutations in the LGI1 gene will develop this form of epilepsy.
Sources
http://www.newswire.ca/releases/May2002/09/c3610.html
http://genetics.nature.com
http://www.efa.org/epusa/061702/hunt.html
MUHC Communications Services (Research)
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