The high frequency of chromosomal copy number variations and candidate genes in epilepsy patients

• Published in: Clinical neurology and neurosurgery 2021-03, Vol.202, p.106487-106487, Article 106487
• Main Authors: Albuz, Burcu, Ozdemir, Ozturk, Silan, Fatma
• Format: Article
• Language: English
• Subjects: aCGH; Adaptor Proteins, Signal Transducing - genetics; Adolescent; Adult; Age; Chemokines, CC - genetics; Child; Child, Preschool; Comparative Genomic Hybridization; Convulsions & seizures; Copy number; Copy number variation; Disease; DNA Copy Number Variations - genetics; DNA Repair Enzymes - genetics; DNA-Binding Proteins - genetics; Epilepsy; Epilepsy - genetics; Etiology; Female; Genes; Genetic Association Studies; Genomes; Genotype & phenotype; GTPase-Activating Proteins - genetics; Humans; Hydrolases - genetics; Infant; Male; Microarray; Nerve Tissue Proteins - genetics; Neurology; Outpatient care facilities; Patients; Phenotypes; Retrospective Studies; Seizure; SOXE Transcription Factors - genetics; Tenascin - genetics; Ubiquitin-Protein Ligases - genetics; Young Adult
• ISSN: 0303-8467; 1872-6968
• DOI: 10.1016/j.clineuro.2021.106487

•Epilepsy is the most common chronic brain disease and affects more than 50 million people worldwide.•The pathogenic or likely pathogenic CNVs associated for epilepsy were detected in 12 patients (15 %).•Epilepsy associated CNVs less than 100 kb were detected in four cases (5%) and these CNVs constituted 13.3 % of all CNVs associated with epilepsy.•MACROD2, ADGRB3(BAI3), SOX8, HIP1,PARK2 and TAFA2 genes were evaluated as potential epilepsy-related genes and NEDD9, RASAL2 and TNR were thought to be the candidate genes for epilepsy. Epilepsy is a chronic brain disease and is estimated to affect more than 50 million people worldwide.Epilepsy is a polygenic and multifactorial disease.Genetic causes play a major role in 40–60 % of all epilepsies.Copy number variations(CNVs) have been reported in approximately 5–12 % of patients with different types of epilepsy.Here we aimed to determine the diagnostic yield of the aCGH in epilepsy and to reveal new candidate genes and CNVs by analyzing aCGH data retrospectively. The clinical data of 80 patients with the diagnosis of epilepsy were examined retrospectively and the raw data of aCGH of these patients were reanalyzed in the light of current literature. Pathogenic/likely pathogenic CNVs were detected in 14 of 80 patients and 12 of these CNVs (15 %) were associated with epilepsy phenotype. In addition, 18 CNVs in 16 different chromosomal loci that were evaluated as the variant of unknown clinical significance(VOUS). In four cases (5%), CNVs associated with epilepsy were less than 100 kb and these accounted for 13.3 % of all epilepsy associated CNVs. The diagnostic yield of aCGH in epilepsy patients was found to be higher than most studies in the literature. MACROD2,ADGRB3(BAI3),SOX8,HIP1,PARK2 and TAFA2 genes were evaluated as potential epilepsy-related genes and NEDD9,RASAL2 and TNR genes thought to be the candidate genes for epilepsy. Our study showed that the diagnostic efficiency of aCGH in epilepsy is high and with more comprehensive studies, it will contribute to the elucidation of genes involved in genetic etiology in epilepsy patients.