[1]董 玲a,谢 云a,杨少青,等.2 例婴儿CDKL5 基因新发突变致早发性癫痫脑病的临床特征与遗传学分析[J].现代检验医学杂志,2022,37(05):50-54+60.[doi:10.3969/j.issn.1671-7414.2022.05.011]
　DONG Linga,XIE Yuna,YANG Shao-qing,et al.Clinical Features and Genetic Analysis of 2 Infant Cases with Early Epileptic Encephalopathies Caused by CDKL5 Gene Novel Mutations[J].Journal of Modern Laboratory Medicine,2022,37(05):50-54+60.[doi:10.3969/j.issn.1671-7414.2022.05.011]
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2 例婴儿CDKL5 基因新发突变致早发性癫痫脑病的临床特征与遗传学分析()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第37卷
期数:
2022年05期
页码:
50-54+60
栏目:
论著
出版日期:
2022-09-15

文章信息/Info

Title:
Clinical Features and Genetic Analysis of 2 Infant Cases with Early Epileptic Encephalopathies Caused by CDKL5 Gene Novel Mutations
文章编号:
1671-7414（2022）05-050-06
作者:
董 玲1a; 谢 云1a; 杨少青2; 刘鸿丽1b; 王 琪3; 宋婷婷1b; 姜永生1b; 张小鸽1b
1. 西北妇女儿童医院a. 检验科；b. 神经内科，西安710061；2. 军事口腔医学国家重点实验室，口腔疾病国家临床医学研究中心，陕西省口腔医学重点实验室/ 空军军医大学口腔医学院口腔罕见病与遗传病门诊/ 口腔生物学教研室，西安710032；3. 西安交通大学第二附属医院检验科，西安710004
Author(s):
DONG Ling1a; XIE Yun1a; YANG Shao-qing2; LIU Hong-li1b; WANG Qi3; SONG Ting-ting1b;  JIANG Yong-sheng1b; ZHANG Xiao-ge1b
1a.Department of Clinical Laboratory；1b. Department of Pediatric Neurology, Northwest Women’s and Children’s Hospital，Xi’an 710061, China；2.State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases/Department of Oral Biology，Clinic of Oral Rare and Genetic Diseases，School of Stomatology/ the Fourth Military Medical University, Xi’an 710032，China；3. Department of Clinical Laboratory，the Second Affiliated Hospital of Xi’an Jiaotong University，Xi’an 710004，China
关键词:
婴儿; 细胞周期蛋白依赖性蛋白激酶5 基因; 新发突变; 早发性癫痫脑病
分类号:
R742.1；Q754
DOI:
10.3969/j.issn.1671-7414.2022.05.011
文献标志码:
A
摘要:
目的　探讨细胞周期蛋白依赖性蛋白激酶5（cyclin-dependent kinase-like 5，CDKL5）基因新发突变导致患儿早发性癫痫脑病的临床特征及分子遗传学特点。方法　收集西北妇女儿童医院儿童神经内科确诊的2 例早发性癫痫脑病患儿的临床资料，应用二代测序技术对核心家系成员进行全外显子测序分析，并用Sanger 测序法进行突变验证。结果　例1 患儿出生后20 天出现强直阵挛、不典型痉挛形式的癫痫发作，两种抗癫痫药物联合治疗后效果较好；例2 患儿出生后1 个月出现全面性强直阵挛发作，并伴显著的上下肢屈曲抖动，进展为难治性痉挛发作及严重精神发育迟滞和语言运动发育障碍，多种抗癫痫药物及生酮饮食联合治疗效果差。两例患儿全基因组基因拷贝数变异（copy numbervariations, CNVs）检测未见明确致病变异。核心家系全外显子组测序结果发现，例1 患儿CDKL5 基因第12 外显子上存在一杂合新发无义突变：NM_003159.2：c.1307C>G（p. Ser436*），其父母该位点未见异常；例2 患儿该基因第13 外显子存在c.1974_1975del（p.Val659GlyfsTer23）新发杂合移码突变，其父母该位点未见异常。根据2015 年美国医学遗传学与基因组学学会（the American College of Medical Genetics and Genomics, ACMG）指南，以上变异均为致病突变。结论　CDKL5 基因c.1307C>G 无义突变和c.1974_1975del 移码突变是先证者早发性癫痫脑病遗传学病因的新发致病变异，扩充了致病基因CDKL5 的基因变异谱。
Abstract:
Objective　To investigate the clinical features and molecular genetic characteristics of cyclin-dependent kinase-like 5 (CDKL5) novel mutations in 2 cases with early epileptic encephalopathies. Methods　The clinical data of two cases with early epileptic encephalopathies in Northwest Women’s and Children’s Hospital of Xi’an were retrospectively analyzed. The whole exome sequencing was performed on the core members of the family, and the characteristics of gene mutations were analyzed by Sanger sequencing. Results　On the 30th day after birth, case one began to have a variety of forms of seizures, such as tonic clonusa and atypical spasm. The child was treated with two kinds of antiepileptic drugs and showed a relatively good therapeutic effect. Case two began to have tonic clonusa seizure on the 30th day after birth, and accompanied by a significant flexion and shaking of upper and lower limbs. The child was treated with a combination of antiepileptic drugs with poor efficacy, which resulted in refractory spasmodic seizures, severe developmental delay and language and motor delay. No pathogenic copy number variations（CNVs） was found in the two cases, while whole exome sequencing identified a nonsense mutation c.1307C>G（p.Ser436*） in CDKL5 in case one, and case two was found to have a de novo frame shift mutation c.1974_1975del（p.Val659GlyfsTer23). The same variants were not found in their parents. According to the 2015 guidelines of the American College of Medical Genetics and Genomics（ACMG）for medical genetics and genomics, all the above mutations are pathogenic mutations. Conclusion　CDKL5 gene nonsense mutation c.1307C >G and frameshift mutation c.1974_ 1975del are new pathogenic variants of the genetic cause of early onset epileptic, which could expand the mutation spectrum of CDKL5 gene.

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备注/Memo

备注/Memo:
作者简介：董玲（1984-），女，本科，主管技师，研究方向：临床检验技术，E-mail：ling.21@qq.com。
通讯作者：张小鸽（1977-），女，本科，研究方向：临床神经病学，E-mail：zxge007@163.com。
更新日期/Last Update: 2022-09-15