AbstractWe present a case of suspected CDKL5 deficiency disorder (CDD) in which a novel intragenic multi-exonic duplication in the CDKL5 gene was identified using next-generation sequencing and multiple ligation-dependent probe amplification. This duplication was assumed to result in a shift of the reading frame and the introduction of a premature stop codon.

摘要我们提出了一例疑似CDKL5缺乏症（CDD）的病例，其中使用下一代测序和多重连接依赖性探针扩增鉴定了CDKL5基因中的新型基因内多外显子重复。假定这种重复会导致阅读框移位并引入过早的终止密码子。

This case highlights the importance of careful phenotyping and comprehensive genetic testing to detect rare structural variants in CDD patients..

该病例突显了仔细的表型分析和全面的基因检测对于检测CDD患者罕见结构变异的重要性。。

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD; OMIM 300672), also known as early infantile epileptic encephalopathy 2, is characterized by severe early-onset drug-resistant epilepsy with motor, cognitive, visual, and autonomic disturbances resulting from nonfunctional or absent CDKL5 protein1.

细胞周期蛋白依赖性激酶样5（CDKL5）缺乏症（CDD；OMIM 300672），也称为早期婴儿癫痫性脑病2，其特征是严重的早发性耐药性癫痫，伴有运动，认知，视觉和自主神经紊乱，由无功能或缺乏CDKL5蛋白1引起。

The prevalence of CDD is estimated at 1 in 40,000–60,000 live births2,3. The CDKL5 gene is located at Xp22.1, and females are more commonly affected than males because of the lethality of germline mutations in most males during fetal development. To date, more than 250 pathogenic CDKL5 variants have been reported; point mutations account for more than half of these variants, with only a few reported intragenic duplications, and detailed clinical information is rarely reported4.

CDD的患病率估计为40000-60000例活产中的1例2,3。CDKL5基因位于Xp22.1，由于大多数男性在胎儿发育过程中生殖系突变的致死性，女性比男性更容易受到影响。迄今为止，已经报道了250多种致病性CDKL5变体；点突变占这些变异的一半以上，只有少数报道的基因内重复，很少报道详细的临床信息4。

Here, we report a novel intragenic multi-exonic duplication in a patient with CDD.An 11-year-old girl was referred to the NHO Shizuoka Institute of Epilepsy and Neurological Disorders. Born at 36 weeks with a birth weight of 2794 g, she was the first child of a nonconsanguineous Japanese couple. Her mother had a history of self-limited epilepsy with centrotemporal spikes (SeLECTS).

在这里，我们报告了CDD患者的新型基因内多外显子重复。一名11岁女孩被转介到NHO静冈癫痫和神经疾病研究所。她出生36周，出生体重2794克，是一对非血缘日本夫妇的第一个孩子。她的母亲有自限性癫痫病史，伴有中央颞尖峰（SeLECTS）。

The neonatal period of the patient was unremarkable; however, at the age of 2 months, she experienced symmetrical bilateral tonic seizures accompanied by upward rolling of the eyeballs and eyelid myoclonia. She developed epileptic spasms (ESs) with series formation at 3 months of age. No dysmorphic features or abnormal laboratory findings were observed.

患者的新生儿期不明显；但是，在2个月大时，她经历了对称的双侧强直性癫痫发作，并伴有眼球向上滚动和眼睑肌阵挛。她在3个月大时出现了癫痫痉挛（ESs），并形成了系列。没有观察到畸形特征或异常的实验室检查结果。

The patient was diagnosed with infantile epileptic spasms syndrome on the basis of ictal electroencephalogram (EEG) findings and hypsarrhythmia. Neither antiepileptic drugs (valproic acid, vitamin B6, zonisamide, levetiracetam, lamotrigine, nitrazepam, and vigaba.

根据发作性脑电图（EEG）发现和心律失常，该患者被诊断出患有婴儿癫痫痉挛综合征。两种抗癫痫药（丙戊酸，维生素B6，唑尼沙胺，左乙拉西坦，拉莫三嗪，硝西泮和维加巴）。

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Download referencesFundingThis work was partly supported by the MHLW Research Program on rare and intractable diseases (grant number JPMH23FC1013).Author informationAuthor notesThese authors contributed equally: Takato Akiba, Shino Shimada.Authors and AffiliationsNHO Shizuoka Institute of Epilepsy and Neurological Disorders, National Epilepsy Center, Shizuoka, JapanTakato Akiba, Shino Shimada & Katsumi ImaiPediatrics and Adolescent Medicine, Juntendo University, Graduate School of Medicine, Tokyo, JapanTakato Akiba & Shino ShimadaDepartment of Clinical Genetics, Juntendo University, Graduate School of Medicine, Tokyo, JapanShino ShimadaDepartment of Pediatrics, Asahikawa Medical University, Asahikawa, JapanSatoru TakahashiAuthorsTakato AkibaView author publicationsYou can also search for this author in.

下载参考文献资助这项工作得到了MHLW罕见和难治性疾病研究计划（资助号JPMH23FC1013）的部分支持。作者信息作者注意到这些作者做出了同样的贡献：Takato Akiba，Shino Shimada。作者和单位日本静冈国立癫痫中心静冈癫痫与神经疾病研究所，静冈，日本秋叶，Shino Shimada＆Katsumi ImaiPediatrics and青春期医学，顺天堂大学，东京医学研究生院，日本秋叶和Shino Shimada顺天堂大学临床遗传学系，东京医学研究生院，日本浅川医科大学儿科系，Asahikawa，JapanSatoru TakahashiAuthorsTakato AkibaView作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarShino ShimadaView author publicationsYou can also search for this author in

PubMed Google ScholarShino ShimadaView作者出版物您也可以在

PubMed Google ScholarKatsumi ImaiView author publicationsYou can also search for this author in

PubMed Google ScholarKatsumi ImaiView作者出版物您也可以在

PubMed Google ScholarSatoru TakahashiView author publicationsYou can also search for this author in

PubMed Google ScholarSatoru TakahashiView作者出版物您也可以在

PubMed Google ScholarContributionsTakato Akiba: writing the original draft, review, and editing. Shino Shimada: writing the original draft, review, and editing. Katsumi Imai: conceptualization, writing, review, and editing. Satoru Takahashi: writing, review, editing, and supervision.

PubMed Google ScholarContributionsTakato Akiba：撰写原稿，评论和编辑。Shino Shimada：撰写原稿，评论和编辑。今井胜美：概念化，写作，评论和编辑。Satoru Takahashi：写作，评论，编辑和监督。

All of the co-authors have read and approved the final manuscript.Corresponding authorCorrespondence to.

所有合著者均已阅读并批准了最终稿件。对应作者对应。

Katsumi Imai.Ethics declarations

今井胜美。道德宣言

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Reprints and permissionsAbout this articleCite this articleAkiba, T., Shimada, S., Imai, K. et al. A case of CDKL5 deficiency disorder with a novel intragenic multi-exonic duplication.

转载和许可本文引用本文Akiba，T.，Shimada，S.，Imai，K。等人的一例CDKL5缺乏症，具有新型基因内多外显子重复。

Hum Genome Var 11, 40 (2024). https://doi.org/10.1038/s41439-024-00296-7Download citationReceived: 30 August 2024Revised: 25 September 2024Accepted: 26 September 2024Published: 08 November 2024DOI: https://doi.org/10.1038/s41439-024-00296-7Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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