{"title":"Autosomal dominant sleep-related hypermotor epilepsy associated with a novel mutation of <i>KCNT1</i>.","authors":"Jinyu Lu, Gaohua Zhao, Dayao Lv, Lanxiao Cao, Guohua Zhao","doi":"10.1515/tnsci-2022-0241","DOIUrl":null,"url":null,"abstract":"<p><p>Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is characterized by severe sleep-related rigid hypermotor seizures. The pathogenic genes of ADSHE include genes encoding subunits of the neuronal nicotinic acetylcholine receptor, <i>KCNT1</i>, <i>DEPDC5</i>, <i>NPRL2/3</i>, <i>CABP4</i>, and <i>CRH.</i> Individuals with <i>KCNT1</i>-related ADSHE are more likely to develop seizures at a younger age, have cognitive comorbidity, and display psychiatric and behavioral problems. In this study, a 12-year-old Chinese girl was referred for genetic evaluation of grand mal seizures. She had paroxysmal convulsions of the limbs and loss of consciousness just after falling asleep without obvious triggers. A novel heterozygous missense mutation c.2797C > T (p.Arg933Cys) in exon 24 of the <i>KCNT1</i> was identified in the proband by whole-exome sequencing and Sanger sequencing, and the clinical symptoms were compatible with ADSHE. The proband's father has been showing similar symptoms for more than 20 years and had the same site mutation. Her mother and sister were physically and genetically normal. The study revealed a novel variant in the <i>KCNT1</i> and expanded the mutation spectrum for this clinical condition. Our results provide further evidence supporting a causative role in <i>KCNT1</i> variants in ADSHE.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9438967/pdf/","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1515/tnsci-2022-0241","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 1
Abstract
Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is characterized by severe sleep-related rigid hypermotor seizures. The pathogenic genes of ADSHE include genes encoding subunits of the neuronal nicotinic acetylcholine receptor, KCNT1, DEPDC5, NPRL2/3, CABP4, and CRH. Individuals with KCNT1-related ADSHE are more likely to develop seizures at a younger age, have cognitive comorbidity, and display psychiatric and behavioral problems. In this study, a 12-year-old Chinese girl was referred for genetic evaluation of grand mal seizures. She had paroxysmal convulsions of the limbs and loss of consciousness just after falling asleep without obvious triggers. A novel heterozygous missense mutation c.2797C > T (p.Arg933Cys) in exon 24 of the KCNT1 was identified in the proband by whole-exome sequencing and Sanger sequencing, and the clinical symptoms were compatible with ADSHE. The proband's father has been showing similar symptoms for more than 20 years and had the same site mutation. Her mother and sister were physically and genetically normal. The study revealed a novel variant in the KCNT1 and expanded the mutation spectrum for this clinical condition. Our results provide further evidence supporting a causative role in KCNT1 variants in ADSHE.
常染色体显性睡眠相关性多运动性癫痫(ADSHE)的特征是严重的睡眠相关性刚性多运动性癫痫发作。ADSHE的致病基因包括神经元烟碱乙酰胆碱受体亚基编码基因KCNT1、DEPDC5、NPRL2/3、CABP4和CRH。患有kcnt1相关ADSHE的个体更有可能在年轻时发生癫痫发作,有认知合并症,并表现出精神和行为问题。在这项研究中,一名12岁的中国女孩被推荐进行大癫痫发作的遗传评估。在没有明显诱因的情况下,她刚入睡就出现了四肢阵发性抽搐和意识丧失。通过全外显子组测序和Sanger测序,在该先证者中发现KCNT1第24外显子一个新的杂合错义突变c.2797C > T (p.a g933cys),临床症状与ADSHE相符。先证者的父亲20多年来一直表现出类似的症状,并且有相同的位点突变。她的母亲和妹妹在身体和基因上都是正常的。该研究揭示了KCNT1的一种新变异,并扩大了这种临床疾病的突变谱。我们的研究结果提供了进一步的证据,支持KCNT1变异在ADSHE中的致病作用。
期刊介绍:
Translational Neuroscience provides a closer interaction between basic and clinical neuroscientists to expand understanding of brain structure, function and disease, and translate this knowledge into clinical applications and novel therapies of nervous system disorders.