{"title":"在一组中国患者中与儿童癫痫相关的HCN1致病变异","authors":"Zhuanyi Yang, Zhuo Kuang, Hongmei Liao, Siyi Gan, Xiaomei Peng, Haiyan Yang, Liwen Wu","doi":"10.1002/epd2.20182","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>HCN ion channel family has a widespread expression in neurons, and recently, increasing studies have demonstrated their roles in epilepsies.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Clinical data of the patients were gathered in a retrospective study. Exon sequencing was used for the patients with unexplained recurrent seizures and varying levels of developmental delay.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>In this study, eight de novo variants of <i>HCN1</i> genes were uncovered in eight patients, including six missense variants, one nonsense variant and one frameshift insertion variant; five of them were reported for the first time. The onset age for eight patients ranges from one month to one year. Their main clinical manifestations are epilepsy and varying degrees of developmental delay, and the main type of seizure is focal secondary generalized tonic–clonic seizure. Importantly, in our study, one case presented with a form of migrating focal seizure that has not been reported in the literature. Seizures from five of the eight children were effectively controlled with antiepileptic drugs including valproic acid, levetiracetam and oxcarbazepine. One child developed normally and four children developed mild delay. One child was treated with topiramate, and the convulsion was partially controlled and showed moderate to severe developmental delay. The antiepileptic treatment failed for the other two children, and the two children were treated with sodium valproate, oxcarbazepine, lamotrigine, chlorbazan, levetiracetam and nitrodiazepam successively, but their convulsions were not controlled and showed moderate to severe developmental delay.</p>\n </section>\n \n <section>\n \n <h3> Significance</h3>\n \n <p>Our research reported eight variants in <i>HCN1</i> gene causing epilepsy; among these variants, five variants were never reported before. <i>HCN1</i>-related epilepsy usually starts infantile period, and focal secondary generalized tonic–clonic seizure is the most common seizure type. Importantly, we reported the case with migrating focal seizure was rarely reported. Our study expanded both genotype and phenotype for <i>HCN1-</i>related epilepsy.</p>\n </section>\n </div>","PeriodicalId":50508,"journal":{"name":"Epileptic Disorders","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"HCN1 pathogenic variants associated with childhood epilepsy in a cohort of Chinese patients\",\"authors\":\"Zhuanyi Yang, Zhuo Kuang, Hongmei Liao, Siyi Gan, Xiaomei Peng, Haiyan Yang, Liwen Wu\",\"doi\":\"10.1002/epd2.20182\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>HCN ion channel family has a widespread expression in neurons, and recently, increasing studies have demonstrated their roles in epilepsies.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Clinical data of the patients were gathered in a retrospective study. Exon sequencing was used for the patients with unexplained recurrent seizures and varying levels of developmental delay.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>In this study, eight de novo variants of <i>HCN1</i> genes were uncovered in eight patients, including six missense variants, one nonsense variant and one frameshift insertion variant; five of them were reported for the first time. The onset age for eight patients ranges from one month to one year. Their main clinical manifestations are epilepsy and varying degrees of developmental delay, and the main type of seizure is focal secondary generalized tonic–clonic seizure. Importantly, in our study, one case presented with a form of migrating focal seizure that has not been reported in the literature. Seizures from five of the eight children were effectively controlled with antiepileptic drugs including valproic acid, levetiracetam and oxcarbazepine. One child developed normally and four children developed mild delay. One child was treated with topiramate, and the convulsion was partially controlled and showed moderate to severe developmental delay. The antiepileptic treatment failed for the other two children, and the two children were treated with sodium valproate, oxcarbazepine, lamotrigine, chlorbazan, levetiracetam and nitrodiazepam successively, but their convulsions were not controlled and showed moderate to severe developmental delay.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Significance</h3>\\n \\n <p>Our research reported eight variants in <i>HCN1</i> gene causing epilepsy; among these variants, five variants were never reported before. <i>HCN1</i>-related epilepsy usually starts infantile period, and focal secondary generalized tonic–clonic seizure is the most common seizure type. Importantly, we reported the case with migrating focal seizure was rarely reported. Our study expanded both genotype and phenotype for <i>HCN1-</i>related epilepsy.</p>\\n </section>\\n </div>\",\"PeriodicalId\":50508,\"journal\":{\"name\":\"Epileptic Disorders\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-11-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Epileptic Disorders\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/epd2.20182\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epileptic Disorders","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/epd2.20182","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
HCN1 pathogenic variants associated with childhood epilepsy in a cohort of Chinese patients
Objective
HCN ion channel family has a widespread expression in neurons, and recently, increasing studies have demonstrated their roles in epilepsies.
Methods
Clinical data of the patients were gathered in a retrospective study. Exon sequencing was used for the patients with unexplained recurrent seizures and varying levels of developmental delay.
Results
In this study, eight de novo variants of HCN1 genes were uncovered in eight patients, including six missense variants, one nonsense variant and one frameshift insertion variant; five of them were reported for the first time. The onset age for eight patients ranges from one month to one year. Their main clinical manifestations are epilepsy and varying degrees of developmental delay, and the main type of seizure is focal secondary generalized tonic–clonic seizure. Importantly, in our study, one case presented with a form of migrating focal seizure that has not been reported in the literature. Seizures from five of the eight children were effectively controlled with antiepileptic drugs including valproic acid, levetiracetam and oxcarbazepine. One child developed normally and four children developed mild delay. One child was treated with topiramate, and the convulsion was partially controlled and showed moderate to severe developmental delay. The antiepileptic treatment failed for the other two children, and the two children were treated with sodium valproate, oxcarbazepine, lamotrigine, chlorbazan, levetiracetam and nitrodiazepam successively, but their convulsions were not controlled and showed moderate to severe developmental delay.
Significance
Our research reported eight variants in HCN1 gene causing epilepsy; among these variants, five variants were never reported before. HCN1-related epilepsy usually starts infantile period, and focal secondary generalized tonic–clonic seizure is the most common seizure type. Importantly, we reported the case with migrating focal seizure was rarely reported. Our study expanded both genotype and phenotype for HCN1-related epilepsy.
期刊介绍:
Epileptic Disorders is the leading forum where all experts and medical studentswho wish to improve their understanding of epilepsy and related disorders can share practical experiences surrounding diagnosis and care, natural history, and management of seizures.
Epileptic Disorders is the official E-journal of the International League Against Epilepsy for educational communication. As the journal celebrates its 20th anniversary, it will now be available only as an online version. Its mission is to create educational links between epileptologists and other health professionals in clinical practice and scientists or physicians in research-based institutions. This change is accompanied by an increase in the number of issues per year, from 4 to 6, to ensure regular diffusion of recently published material (high quality Review and Seminar in Epileptology papers; Original Research articles or Case reports of educational value; MultiMedia Teaching Material), to serve the global medical community that cares for those affected by epilepsy.