The publication of recent papers by Mefford et al.  and Cooper et al.  brought up an interesting issue again concerning the role of the 15q13.3 microduplication. While the 15q13.3 microdeletion is a well-established risk factor for epilepsy, particularly, idiopathic generalised (genetic generalised epilepsy), the role of the reciprocal microduplication is not clear. In two epilepsy cohorts this microduplication is absent in 1223 IGE patients , 517 epilepsy patients  and 315 patients with epileptic encephalopathies .
This variant is seen in two control cohorts at a frequency of 0.5% (2/3699, 3/8329) [2, 3] and in a mixed cohort of patients with intellectual disability at 0.13% (20/15,767) , the absence in IGE and other pure epilepsy cohorts is intriguing (Table 1).
Neither comparison between two groups using a Fisher’s exact test is significant, given that it is conceptually difficult to arrive at statistical significant results with very small frequencies. However, comparing these three frequencies using a Chi square test, the differences are significant at p=0.02. Accordingly, this might indicate that the 15q13.3 microduplication is a protective factor against epilepsy or the differences are due to ascertainment bias.
1. Mefford, H., Rare copy number variants are an important cause of epileptic encephalopathies. 2011.
2. Cooper, G.M., et al., A copy number variation morbidity map of developmental delay. Nat Genet, 2011. 43(9): p. 838-46.
3. Helbig, I., et al., 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat Genet, 2009. 41(2): p. 160-2.
4. Mefford, H.C., et al., Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies. PLoS Genet, 2010. 6(5): p. e1000962.
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Helbig, I. Does the 15q13.3 microduplication protect against epilepsy?. Retrieved [enter date], from http://www.euroepinomics.wordpress.com