Xuechao Zhao1, Haofeng Ning2, Yanhong Wang3, Ganye Zhao1, Shiyue Mei3, Ning Liu1, Conghui Wang1, Aojie Cai4, Erhu Wei5, Xiangdong Kong6. 1. The Genetics and Prenatal Diagnosis Center, The Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Jianshe Rd, Erqi District, Zhengzhou, 450052, Henan, China. 2. Department of Medical Genetics and Antenatal Diagnosis, Luoyang Maternal and Child Health Care Hospital, Luoyang, 471000, Henan, China. 3. Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated To Zhengzhou University, Zhengzhou Children's Hospital, No-33, Longhu Waihuan East road, Zhengzhou, 450018, Henan, China. 4. Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China. 5. Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Jianshe Rd, Erqi District, Zhengzhou, 450052, Henan, China. 6. The Genetics and Prenatal Diagnosis Center, The Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Jianshe Rd, Erqi District, Zhengzhou, 450052, Henan, China. kxd1968@163.com.
Abstract
OBJECTIVES: We aimed to investigate the genetic etiology of epilepsy in children, and to analyze the nature of genetic variation, the function of related genes, and the genotype-phenotype relationship. Moreover, the impact of the genetic diagnosis on prognosis and prenatal diagnosis will be discussed. METHODS: We recruited 218 pediatric epilepsy patients with onset ages ranging from postnatal 5 days to 3 years during a three-year collection period. WES was conducted only for the probands to screen for possible candidate genes. RESULTS: A total of 55 patients (25.2%) had positive genetic diagnoses. Autosomal dominant gene variants were the most common (34/55; 61.8%) and de novo variants (31/34; 91.2%) consistent with an autosomal dominant mode of inheritance. Among 64 variants identified in 35 genes, 33 (51.6%) were novel, previously unreported. Ion channel genes play critical roles in the pathogenesis of epilepsy, accounting for 58.8% (20/34) of the variants. A total of 31 (56.4%) families chose to have a prenatal diagnosis in subsequent pregnancies based on the genetic diagnosis. CONCLUSION: Our data suggest that applying WES in patients with epilepsy of unknown etiology can improve counseling and management. Early establishment of genetic diagnosis was necessary for counseling on recurrence risk and prenatal diagnosis. A large number of unreported variants were detected, widening the known spectrum of genetic variation related to epilepsy risk.
OBJECTIVES: We aimed to investigate the genetic etiology of epilepsy in children, and to analyze the nature of genetic variation, the function of related genes, and the genotype-phenotype relationship. Moreover, the impact of the genetic diagnosis on prognosis and prenatal diagnosis will be discussed. METHODS: We recruited 218 pediatric epilepsy patients with onset ages ranging from postnatal 5 days to 3 years during a three-year collection period. WES was conducted only for the probands to screen for possible candidate genes. RESULTS: A total of 55 patients (25.2%) had positive genetic diagnoses. Autosomal dominant gene variants were the most common (34/55; 61.8%) and de novo variants (31/34; 91.2%) consistent with an autosomal dominant mode of inheritance. Among 64 variants identified in 35 genes, 33 (51.6%) were novel, previously unreported. Ion channel genes play critical roles in the pathogenesis of epilepsy, accounting for 58.8% (20/34) of the variants. A total of 31 (56.4%) families chose to have a prenatal diagnosis in subsequent pregnancies based on the genetic diagnosis. CONCLUSION: Our data suggest that applying WES in patients with epilepsy of unknown etiology can improve counseling and management. Early establishment of genetic diagnosis was necessary for counseling on recurrence risk and prenatal diagnosis. A large number of unreported variants were detected, widening the known spectrum of genetic variation related to epilepsy risk.
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