25 January 2009
Epilepsy is a neurological condition where individuals are affected by recurrent seizures that correlate with periods of abnormal brain activity. There are various known causes of epilepsy, such as brain damage or a brain tumour, and these are termed symptomatic epilepsy; however, the majority of cases are termed idiopathic epilepsy, having no known root cause. The idiopathic generalized epilepsies (IGE) account for up to a third of all epilepsies, and epidemiological evidence has suggested that they involve complex genetic contributions (see previous news). Now a new paper in the journal Nature Genetics reports an association between microdeletions in a region on chromosome 15 and IGE.
Previous research has suggested that the 15q13-q14 region of chromosome 15 may be involved in epilepsy; susceptibility loci for common IGE syndromes have been mapped to the region, and deletions have been associated with various neuropsychiatric conditions, including epilepsy, autism and schizophrenia. The authors of this new study tested the 15q13.3 region in two independent groups of individuals with IGE and matched controls. The research project was part of EPICURE, an international collaborative research project to study the genomics and neurobiology of epilepsy, with a view to developing novel therapeutic interventions
Together, more than 1,200 individuals with IGE and over 3,600 matched controls were screened. A total of 12 IGE patients were found to have microdeletions in the 15q13.3 region, but none of the controls. This deletion was calculated to be around around fifty times more frequent in IGE than in the general population,
This finding strengthens previous observations of a link between microdeletions in this region of chromosome 15 and idiopathic epilepsy; however, there was not the same association with other neuropsychiatric symptoms previously documented. The phenotype of individuals with the microdeletion varied; a variable degree of intellectual disability was observed in three, but the other nine had neither intellectual disability nor dysmorphic features, and none had any history of psychosis. In addition to identifying the most prevalent genetic risk factor for IGE thus far, the authors also conclude that their findings “imply that shared mechanisms are involved in the pathogenesis of a spectrum of seemingly unrelated neuropsychiatric disorders, and argue for a new framework for understanding complex genetic diseases” [Helbig I et al. (2009) Nat Genet. Jan 11, Epub ahead of print].
Comment: The chromosome 15 region linked with a common, complex form of epilepsy differs from previous genetic susceptibility regions, which have been associated with rare, inherited forms of epilepsy. The implication of structural variants (in this case, microdeletions) as opposed to sequence variants with a complex form of disease is of particular interest. However, the interplay of genetic factors in determining the phenotype of epilepsy, learning disability and neuropsychiatric conditions is likely to prove extremely difficult to decipher.