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

2015-11

Damiano, John A

Mullen, Saul A

Hildebrand, Michael S

Bellows, Susannah T

Lawrence, Kate M

Arsov, Todor

Dibbens, Leanne M

Major, Heather

Dahl, Hans-Henrik M

Mefford, Heather C

Darbro, Benjamin W

Scheffer, Ingrid E

Berkovic, Samuel F

Epilepsy, Generalized--Genetics

alpha7 Nicotinic Acetylcholine Receptor--Genetics

Genetic predispositio to disease

Alleles

Journal Article

0000-0002-2311-2174

0000-0003-4580-841X

10.1016/j.eplepsyres.2015.09.007

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.

link

Epilepsy Research 2015; 117: 70-73

Epilepsy Research