Genetic neonatal seizures in the neonatal intensive care unit: Diagnostic and prognostic implications for three families.

IF 1.9 4区医学 Q3 CLINICAL NEUROLOGY Epileptic Disorders Pub Date : 2024-11-21 DOI:10.1002/epd2.20315

Rongrong Chen, Huiming Wu, Yi Lu, Honggang Yin, Xueqian Wang, Xiaohua Zhang

{"title":"Genetic neonatal seizures in the neonatal intensive care unit: Diagnostic and prognostic implications for three families.","authors":"Rongrong Chen, Huiming Wu, Yi Lu, Honggang Yin, Xueqian Wang, Xiaohua Zhang","doi":"10.1002/epd2.20315","DOIUrl":null,"url":null,"abstract":"Objective: We investigated neonatal seizures in three probands admitted to the neonatal intensive care units and their affected family members.Methods: Whole exome sequencing (WES) was performed along with confirmation by Sanger sequencing and segregation analysis. Copy number variant (CNV) analysis was also conducted. Neuroimaging, electroencephalography, and metabolic analysis revealed clinical phenotypes.Results: Bi-allelic variants c.1025T>C and c.1150G>A in MOCS1 were found in twin girls with molybdenum cofactor deficiency. The c.1025T>C variant was novel. A c.877C>T variant in KCNQ2 co-segregated with seizures in a family. A de novo 6.25 Mb duplication on 2q24.3 encompassing SCN1A, SCN2A, and SCN3A was identified in a proband who demonstrated normal development without seizures on follow-up.Significance: WES facilitated the molecular diagnosis of neonatal seizures in the study participants. Variants in the KCNQ2 and MOCS1 genes were classified as likely pathogenic based on our findings. The individual with a duplication of the sodium channel gene cluster on 2q24.3 exhibited additional phenotypes. Our investigation expanded the genotype-phenotype spectrum.","PeriodicalId":50508,"journal":{"name":"Epileptic Disorders","volume":" ","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epileptic Disorders","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/epd2.20315","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: We investigated neonatal seizures in three probands admitted to the neonatal intensive care units and their affected family members.

Methods: Whole exome sequencing (WES) was performed along with confirmation by Sanger sequencing and segregation analysis. Copy number variant (CNV) analysis was also conducted. Neuroimaging, electroencephalography, and metabolic analysis revealed clinical phenotypes.

Results: Bi-allelic variants c.1025T>C and c.1150G>A in MOCS1 were found in twin girls with molybdenum cofactor deficiency. The c.1025T>C variant was novel. A c.877C>T variant in KCNQ2 co-segregated with seizures in a family. A de novo 6.25 Mb duplication on 2q24.3 encompassing SCN1A, SCN2A, and SCN3A was identified in a proband who demonstrated normal development without seizures on follow-up.

Significance: WES facilitated the molecular diagnosis of neonatal seizures in the study participants. Variants in the KCNQ2 and MOCS1 genes were classified as likely pathogenic based on our findings. The individual with a duplication of the sodium channel gene cluster on 2q24.3 exhibited additional phenotypes. Our investigation expanded the genotype-phenotype spectrum.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

新生儿重症监护室中的遗传性新生儿癫痫：对三个家庭的诊断和预后影响。

目的我们调查了新生儿重症监护室收治的三位疑似患者及其受影响家庭成员的新生儿癫痫发作情况：方法：进行了全外显子组测序（WES），并通过桑格测序和分离分析进行了确认。还进行了拷贝数变异（CNV）分析。神经影像学、脑电图和代谢分析显示了临床表型：结果：在患有钼辅助因子缺乏症的双胞胎女孩中发现了 MOCS1 的 c.1025T>C 和 c.1150G>A 双等位基因变异。c.1025T>C变异是新发现的。在一个家族中，KCNQ2的c.877C>T变异与癫痫发作共分离。在一名疑似患者身上发现了 2q24.3 上 6.25 Mb 的新重复序列，其中包括 SCN1A、SCN2A 和 SCN3A，该患者发育正常，随访时无癫痫发作：WES有助于对研究对象的新生儿癫痫发作进行分子诊断。根据我们的研究结果，KCNQ2 和 MOCS1 基因的变异被归类为可能致病。2q24.3上钠离子通道基因簇重复的个体表现出额外的表型。我们的调查扩大了基因型-表型谱。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Epileptic Disorders 医学-临床神经学

CiteScore

4.10

自引率

8.70%

发文量

138

审稿时长

6-12 weeks

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.