Abstract：
OBJECTIVE: To explore the clinical features and genetic basis for a child with Intellectual developmental disorder (IDD) and epilepsy.
METHODS: A child who was admitted to the Children\'s Medical Center of the Affiliated Hospital of Guangdong Medical University in February 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.
RESULTS: The patient, a 3-month-and-27-day female infant, had developed the symptoms in the neonatal period, which included severe developmental delay, respiratory difficulties and pauses, increased muscle tone of four limbs, feeding difficulty, and seizures. Cerebral MRI revealed bilateral cerebellar hypoplasia, and video EEG showed slightly increased sharp waves emanating predominantly from the right parietal, occipital, and posterior temporal regions. WES revealed that she has harbored a missense c.3196G>A (p.Glu1066Lys) variant of the CLTC gene, which was confirmed to be de novo by Sanger sequencing. Based on the guideline from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS2+PM2_Supporting+PP3).
CONCLUSIONS: The c.3196G>A (p.Glu1066Lys) missense variant of the CLTC gene probably underlay the pathogenesis in this child. Above finding has facilitated her diagnosis and treatment.
METHODS: A child who was admitted to the Children\'s Medical Center of the Affiliated Hospital of Guangdong Medical University in February 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.
RESULTS: The patient, a 3-month-and-27-day female infant, had developed the symptoms in the neonatal period, which included severe developmental delay, respiratory difficulties and pauses, increased muscle tone of four limbs, feeding difficulty, and seizures. Cerebral MRI revealed bilateral cerebellar hypoplasia, and video EEG showed slightly increased sharp waves emanating predominantly from the right parietal, occipital, and posterior temporal regions. WES revealed that she has harbored a missense c.3196G>A (p.Glu1066Lys) variant of the CLTC gene, which was confirmed to be de novo by Sanger sequencing. Based on the guideline from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS2+PM2_Supporting+PP3).
CONCLUSIONS: The c.3196G>A (p.Glu1066Lys) missense variant of the CLTC gene probably underlay the pathogenesis in this child. Above finding has facilitated her diagnosis and treatment.
摘要：
目的：探讨1例智力发育障碍(IDD)合并癫痫患儿的临床特征和遗传基础。
方法：选取广东医科大学附属医院儿童医学中心2021年2月收治的儿童作为研究对象。收集患儿的临床资料。收集儿童及其父母的外周血样本并进行全外显子组测序(WES)。通过Sanger测序验证候选变体。
结果：患者，一个3个月27天的女婴,在新生儿期出现了症状，其中包括严重的发育迟缓，呼吸困难和停顿，增加了四肢的肌肉张力，喂养困难，和癫痫发作。脑MRI显示双侧小脑发育不全，视频脑电图显示，主要来自右顶叶的尖锐波略有增加，枕骨,和后颞区。WES透露，她有一个误解c.3196G>A(p。Glu1066Lys）CLTC基因的变体，通过Sanger测序证实是从头的。根据美国医学遗传学和基因组学学院（ACMG）的指南，该变异体被分类为可能致病(PS2+PM2_支持+PP3)。
结论：c.3196G>A（p。Glu1066Lys）CLTC基因的错义变异可能是该儿童发病机理的基础。上述发现促进了她的诊断和治疗。
方法：选取广东医科大学附属医院儿童医学中心2021年2月收治的儿童作为研究对象。收集患儿的临床资料。收集儿童及其父母的外周血样本并进行全外显子组测序(WES)。通过Sanger测序验证候选变体。
结果：患者，一个3个月27天的女婴,在新生儿期出现了症状，其中包括严重的发育迟缓，呼吸困难和停顿，增加了四肢的肌肉张力，喂养困难，和癫痫发作。脑MRI显示双侧小脑发育不全，视频脑电图显示，主要来自右顶叶的尖锐波略有增加，枕骨,和后颞区。WES透露，她有一个误解c.3196G>A(p。Glu1066Lys）CLTC基因的变体，通过Sanger测序证实是从头的。根据美国医学遗传学和基因组学学院（ACMG）的指南，该变异体被分类为可能致病(PS2+PM2_支持+PP3)。
结论：c.3196G>A（p。Glu1066Lys）CLTC基因的错义变异可能是该儿童发病机理的基础。上述发现促进了她的诊断和治疗。
