KCNB1 frameshift variant caused inherited intellectual disability, developmental delay, and seizure.

IF 1.1 Q2 MEDICINE, GENERAL & INTERNAL
Eyyup Uctepe, Fatma Nisa Esen, Sait Tümer, Hanifenur Mancılar, Ahmet Yeşilyurt
{"title":"KCNB1 frameshift variant caused inherited intellectual disability, developmental delay, and seizure.","authors":"Eyyup Uctepe,&nbsp;Fatma Nisa Esen,&nbsp;Sait Tümer,&nbsp;Hanifenur Mancılar,&nbsp;Ahmet Yeşilyurt","doi":"10.5582/irdr.2022.01096","DOIUrl":null,"url":null,"abstract":"<p><p>Potassium voltage-gated channel subfamily B member 1 (<i>KCNB1</i>) encodes Kv2.1 potassium channel. KCNB1 mutations are known to cause global developmental delay, behavioral disorders, and various epilepsies. Most variants occur de novo and are rarely inherited. Here, we report a 14-year-old male patient who was admitted to our clinic with seizures, developmental delay history, and intellectual disability. Brain magnetic resonance image (MRI) was normal and electroencephalogram (EEG) showed spike and sharp-wave complexes emerging in the left hemisphere parietooccipital areas, which were paroxysmally generalized. We performed whole exome sequence analysis (WES) and identified a heterozygous frameshift mutation c.522delA in exon 1 of <i>KCNB1</i> (NM_004975.4) predicting a premature stop codon p.Lys174Asnfs*20 in the proband. Sanger sequencing confirmed the heterozygous c.522delA mutation in the proband and his mother who also had epilepsy and learning difficulties. His 45 year old mother had used antiepileptic drugs for 9 years after a seizure episode at 12 years old. Also, his mother's uncle's son is nonverbal and has developmental delay and epilepsy. Our study shows that frameshift mutation cytoplasmic domain of <i>KCNB1</i> gene can cause intrafamilial phenotypic variability and relatively mild clinical findings in these patients.</p>","PeriodicalId":14420,"journal":{"name":"Intractable & rare diseases research","volume":null,"pages":null},"PeriodicalIF":1.1000,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709620/pdf/irdr-11-219.pdf","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Intractable & rare diseases research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5582/irdr.2022.01096","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 1

Abstract

Potassium voltage-gated channel subfamily B member 1 (KCNB1) encodes Kv2.1 potassium channel. KCNB1 mutations are known to cause global developmental delay, behavioral disorders, and various epilepsies. Most variants occur de novo and are rarely inherited. Here, we report a 14-year-old male patient who was admitted to our clinic with seizures, developmental delay history, and intellectual disability. Brain magnetic resonance image (MRI) was normal and electroencephalogram (EEG) showed spike and sharp-wave complexes emerging in the left hemisphere parietooccipital areas, which were paroxysmally generalized. We performed whole exome sequence analysis (WES) and identified a heterozygous frameshift mutation c.522delA in exon 1 of KCNB1 (NM_004975.4) predicting a premature stop codon p.Lys174Asnfs*20 in the proband. Sanger sequencing confirmed the heterozygous c.522delA mutation in the proband and his mother who also had epilepsy and learning difficulties. His 45 year old mother had used antiepileptic drugs for 9 years after a seizure episode at 12 years old. Also, his mother's uncle's son is nonverbal and has developmental delay and epilepsy. Our study shows that frameshift mutation cytoplasmic domain of KCNB1 gene can cause intrafamilial phenotypic variability and relatively mild clinical findings in these patients.

KCNB1移码变体可导致遗传性智力残疾、发育迟缓和癫痫发作。
钾电压门控通道亚家族B成员1 (KCNB1)编码Kv2.1钾通道。已知KCNB1突变可导致整体发育迟缓、行为障碍和各种癫痫。大多数变异都是从头开始的,很少遗传。在这里,我们报告一位14岁的男性患者,他因癫痫发作、发育迟缓史和智力残疾而入院。脑磁共振(MRI)检查正常,脑电图(EEG)显示左半球顶枕区出现突波和锐波复合物,呈阵发性广泛性。我们进行了全外显子序列分析(WES),在KCNB1 (NM_004975.4)的外显子1中发现了一个杂合移码突变c.522delA,预测了先证子中过早停止密码子p.Lys174Asnfs*20。桑格测序证实了先证和他患有癫痫和学习困难的母亲的杂合c.522delA突变。他45岁的母亲在12岁时癫痫发作后服用了9年的抗癫痫药物。而且,他母亲的叔叔的儿子不会说话,有发育迟缓和癫痫。我们的研究表明,KCNB1基因胞质结构域移码突变可导致这些患者的家族内表型变异和相对轻微的临床表现。
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 求助全文
来源期刊
Intractable & rare diseases research
Intractable & rare diseases research MEDICINE, GENERAL & INTERNAL-
CiteScore
2.10
自引率
0.00%
发文量
29
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信