Uncovering genomic causes of co-morbidity in epilepsy: gene-driven phenotypic characterization of rare microdeletions.
Kasperavičiūtė D., Catarino CB., Chinthapalli K., Clayton LMS., Thom M., Martinian L., Cohen H., Adalat S., Bockenhauer D., Pope SA., Lench N., Koltzenburg M., Duncan JS., Hammond P., Hennekam RCM., Land JM., Sisodiya SM.
BACKGROUND: Patients with epilepsy often suffer from other important conditions. The existence of such co-morbidities is frequently not recognized and their relationship with epilepsy usually remains unexplained. METHODOLOGY/PRINCIPAL FINDINGS: We describe three patients with common, sporadic, non-syndromic epilepsies in whom large genomic microdeletions were found during a study of genetic susceptibility to epilepsy. We performed detailed gene-driven clinical investigations in each patient. Disruption of the function of genes in the deleted regions can explain co-morbidities in these patients. CONCLUSIONS/SIGNIFICANCE: Co-morbidities in patients with epilepsy can be part of a genomic abnormality even in the absence of (known) congenital malformations or intellectual disabilities. Gene-driven phenotype examination can also reveal clinically significant unsuspected condition.