Evaluation of multiple putative risk alleles within the 15q13.3 region for genetic generalized epilepsy

• Published in: Epilepsy research Vol. 117; pp. 70 - 73
• Main Authors: Damiano, John A., Mullen, Saul A., Hildebrand, Michael S., Bellows, Susannah T., Lawrence, Kate M., Arsov, Todor, Dibbens, Leanne, Major, Heather, Dahl, Hans-Henrik M., Mefford, Heather C., Darbro, Benjamin W., Scheffer, Ingrid E., Berkovic, Samuel F.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2015
• Subjects: Alleles; alpha7 Nicotinic Acetylcholine Receptor - genetics; Chromosomes, Human, Pair 15; Complex traits; DNA Copy Number Variations; Epilepsy and seizures; Epilepsy, Generalized - genetics; Female; Gene Frequency; Genetic Loci; Genetic Predisposition to Disease; Genetics; Humans; Male; Molecular genetics; Neurology; Pedigree; Polymorphism, Genetic; Neurology; Genetics; Epilepsy and seizures; Molecular genetics; Complex traits
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/j.eplepsyres.2015.09.007

•Genetic analysis of patients with generalized epilepsy was performed.•Three missense variants in CHRNA7 and CHRFAM7A were found.•The common 2-bp deletion in CHRFAM7A was not enriched in patients.•Missense variants contribute to complex inheritance in generalized epilepsy. The chromosome 15q13.3 region has been implicated in epilepsy, intellectual disability and neuropsychiatric disorders, especially schizophrenia. Deficiency of the acetylcholine receptor gene CHRNA7 and the partial duplication, CHRFAM7A, may contribute to these phenotypes and we sought to comprehensively analyze these genes in genetic generalized epilepsy. We analyzed using DHPLC, Sanger sequencing and long range PCR, 174 probands with genetic generalized epilepsy with or without intellectual disability or psychosis, including 8 with the recurrent 15q13.3 microdeletion. We searched CHRNA7 and CHRFAM7A for single sequence variants, small copy number variants, and the common 2-bp deletion in CHRFAM7A. We identified two novel and one reported missense variants. The common 2-bp deletion was not enriched in patients compared to controls. Our data suggest that missense mutations in CHRNA7 contribute to complex inheritance in genetic generalized epilepsy in a similar fashion to the 15q13.3 microdeletion. They do not support a pathogenic role for the common 2-bp CHRFAM7A deletion.