February 5, 2009
Missing piece in chromosome increases epilepsy risk
Tiny deletions in a section of human chromosome 15 are linked to an increased risk of idiopathic generalized epilepsies, according to results of a multi-center study published this month in Nature Genetics. These forms of seizure disorders account for about a third of all epilepsies. The findings, the authors noted, suggests that microdeletions in a genetic hotspot known as 15q13.3 are the most prevalent risk factor for common epilepsies discovered so far.
The international team of scientists, led by Thomas Sandler of the University of Cologne, Germany, included UW researchers Heather Mefford, former medical genetics fellow and now acting assistant professor of pediatrics; Andrew Sharp, a former UW Rosetta Fellow now at the University of Geneva; and Evan Eichler, professor of genome sciences and a member of the Howard Hughes Medical Institute.
The critical region of the deletions on 15q13.3 contains at least seven genes. The one that codes for a subunit of the nicotinergic acetylcholine receptor is the most likely suspect for idiopathic generalized epilepsies, according to the researchers. Receptors with this subunit are thought to help excite or quiet nerve cells.
An earlier study from the Eichler lab identified microdeletions on 15q13.3 in patients with mental retardation accompanied by epilepsy, and other studies have found the deletion in schizophrenia, autism, and other brain disorders. In this study, most deletion carriers with common idiopathic epilepsy did not have any neuropsychiatric conditions previously associated with 15q13.3 microdeletions.
The authors pointed to the wide variability in the effects of 15q13.3 microdeletions. Some people missing tiny pieces of the gene sequence are healthy and apparently unaffected. Others have neuropsychiatric impairments of various types and of varying degrees, from mild to severe. These findings, the researchers suggested, imply that shared biological mechanisms are behind seemingly unrelated neuropsychiatric disorders.
