A 1.36-megabase deletion in chromosome 18q21.32 including GRP in a patient with epilepsy, borderline intellectual disability, and multiple cerebral cavernous malformations

Abstract

From analysis of copy number variations (CNVs) in a genome-wide association study (GWAS) of symptomatic epilepsy, we discovered a 1.36 megabase deletion at chromosome 18q21.32 in a patient with borderline intellectual disability, multiple cerebral cavernous malformations (CMs), and complex partial seizures from age one year. The deletion was confirmed by quantitative polymerase chain reaction. The deleted region included the genes ALPK2, MALT1, ZNF532, GRP, RAX, CPLX4, LMAN1, and CCBE1 . GRP (gastrin-releasing peptide, or bombesin) and GRP receptor are expressed in the hippocampus, where GRP depolarizes GABAergic interneurons, thus inhibiting CA1 pyramidal neurons and suppressing seizures. G..