Epilepsy phenotype and gene ontology analysis of the 129 genes in a large neurodevelopmental disorders cohort

Frontiers in Neurology

Neurology

Hyeji Jun¹  Jihoon G. Yoon²  Seungbok Lee²  Man Jin Kim²  Young Jun Ko³  Ki Joong Kim⁴  Byung Chan Lim⁴  Soo Yeon Kim⁵  Jong-Hee Chae⁵  Kwangsoo Kim⁶  Hunmin Kim⁶ 

[1] Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea;Department of Genomic Medicine, Seoul National University Hospital, Seoul, Republic of Korea;Department of Pediatrics, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Republic of Korea;Department of Pediatrics, Pediatric Neuroscience Center, Seoul National University Children's Hospital, Seoul, Republic of Korea;Department of Pediatrics, Pediatric Neuroscience Center, Seoul National University Children's Hospital, Seoul, Republic of Korea;Department of Genomic Medicine, Seoul National University Hospital, Seoul, Republic of Korea;Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Republic of Korea;

关键词: neurodevelopmental disorders;    epilepsy;    genetic testing;    gene ontology;    seizure;   

DOI  :  10.3389/fneur.2023.1218706

 received in 2023-05-08, accepted in 2023-07-19,  发布年份 2023

来源: Frontiers

【 摘 要 】

ObjectiveAlthough pediatric epilepsy is an independent disease entity, it is often observed in pediatric neurodevelopmental disorders (NDDs) as a major or minor clinical feature, which might provide diagnostic clues. This study aimed to identify the clinical and genetic characteristics of patients with epilepsy in an NDD cohort and demonstrate the importance of genetic testing.MethodsWe retrospectively analyzed the detailed clinical differences of pediatric NDD patients with epilepsy according to their genetic etiology. Among 1,213 patients with NDDs, 477 were genetically diagnosed by exome sequencing, and 168 had epilepsy and causative variants in 129 genes. Causative genes were classified into two groups: (i) the “epilepsy-genes” group resulting in epilepsy as the main phenotype listed in OMIM, Epi25, and ClinGen (67 patients) and (ii) the “NDD-genes” group not included in the “epilepsy-genes” group (101 patients).ResultsPatients in the “epilepsy-genes” group started having seizures, often characterized by epilepsy syndrome, at a younger age. However, overall clinical features, including treatment responses and all neurologic manifestations, showed no significant differences between the two groups. Gene ontology analysis revealed the close interactions of epilepsy genes associated with ion channels and neurotransmitters.ConclusionWe demonstrated a similar clinical presentation of different gene groups regarding biological/molecular processes in a large NDDs cohort with epilepsy. Phenotype-driven genetic analysis should cover a broad scope, and further studies are required to elucidate integrated pathomechanisms.

【 授权许可】

Unknown   
Copyright © 2023 Ko, Kim, Lee, Yoon, Kim, Jun, Kim, Chae, Kim, Kim and Lim.