Abstract：
BACKGROUND: Epilepsy is a common multifactorial neurological disease usually diagnosed during childhood. In this study, we present the contribution of consecutive genetic testing to the genetic diagnostic yield of childhood epilepsy.
METHODS: In 100 children (53 female, 47 male) with epilepsy, targeted sequencing (TS) and clinical exome sequencing (CES) were performed. All cases (n = 100) included in the study were epilepsy patients. In addition, we investigated the genetic diagnosis rates according to the associated co-occurring findings (including developmental delay/intellectual disability, brain malformations, macro-/microcephaly, and dysmorphic features).
RESULTS: The overall diagnostic rate in this study was 33% (n = 33 patients). We identified 11 novel variants in WDR45, ARX, PCDH19, SCN1A, CACNA1A, LGI1, ASPM, MECP2, NF1, TSC2, and CDK13. Genetic diagnosis rates were as follows: cases with developmental delay/intellectual disability 38.7% (24/62) and without developmental delay/intellectual disability 23.6% (9/38); cases with brain malformations 46.8% (15/32) and without brain malformations 25% (16/64); cases with macro-/microcephaly 50% (6/12) and without macro-/microcephaly 28.4% (25/88); and cases with dysmorphic features 48.2% (14/29) and without dysmorphic features 23.9% (17/71).
CONCLUSIONS: Genotype-phenotype correlation is even more important in diseases such as epilepsy, which include many genes and variants of these genes in etiopathogenesis. We presented the clinical findings of the cases carrying 11 novel variants in detail, including dysmorphic features, accompanying neurodevelopmental disorders, EEG results, and brain MRI results.
METHODS: In 100 children (53 female, 47 male) with epilepsy, targeted sequencing (TS) and clinical exome sequencing (CES) were performed. All cases (n = 100) included in the study were epilepsy patients. In addition, we investigated the genetic diagnosis rates according to the associated co-occurring findings (including developmental delay/intellectual disability, brain malformations, macro-/microcephaly, and dysmorphic features).
RESULTS: The overall diagnostic rate in this study was 33% (n = 33 patients). We identified 11 novel variants in WDR45, ARX, PCDH19, SCN1A, CACNA1A, LGI1, ASPM, MECP2, NF1, TSC2, and CDK13. Genetic diagnosis rates were as follows: cases with developmental delay/intellectual disability 38.7% (24/62) and without developmental delay/intellectual disability 23.6% (9/38); cases with brain malformations 46.8% (15/32) and without brain malformations 25% (16/64); cases with macro-/microcephaly 50% (6/12) and without macro-/microcephaly 28.4% (25/88); and cases with dysmorphic features 48.2% (14/29) and without dysmorphic features 23.9% (17/71).
CONCLUSIONS: Genotype-phenotype correlation is even more important in diseases such as epilepsy, which include many genes and variants of these genes in etiopathogenesis. We presented the clinical findings of the cases carrying 11 novel variants in detail, including dysmorphic features, accompanying neurodevelopmental disorders, EEG results, and brain MRI results.
摘要：
背景：癫痫是一种常见的多因素神经系统疾病，通常在儿童时期诊断。在这项研究中,我们介绍了连续基因检测对儿童癫痫基因诊断率的贡献.
方法：在100名儿童中（53名女性，47名男性）患有癫痫，进行靶向测序(TS)和临床外显子组测序(CES)。纳入研究的所有病例（n=100）均为癫痫患者。此外,我们根据相关的共同发生的发现（包括发育迟缓/智力障碍，大脑畸形,大头/小头畸形，和变形特征)。
结果：本研究的总诊断率为33%（n=33例）。我们在WDR45、ARX、PCDH19,SCN1A,CACNA1A,LGI1、ASPM、MECP2、NF1、TSC2和CDK13。基因诊断率如下：发育迟缓/智力残疾的病例38.7％（24/62），无发育迟缓/智力残疾的病例23.6％（9/38）；脑畸形的病例46.8％（15/32），无脑畸形的病例25％（16/64）；大头/小头畸形的病例50％（6/12），无大/小头/小头畸形的病例28.4％（25/88）；
结论：基因型-表型相关性在癫痫等疾病中更为重要。其中包括许多基因和这些基因的变异。我们详细介绍了携带11个新变体的病例的临床发现，包括畸形特征，伴随神经发育障碍，脑电图结果,和脑部MRI结果。
方法：在100名儿童中（53名女性，47名男性）患有癫痫，进行靶向测序(TS)和临床外显子组测序(CES)。纳入研究的所有病例（n=100）均为癫痫患者。此外,我们根据相关的共同发生的发现（包括发育迟缓/智力障碍，大脑畸形,大头/小头畸形，和变形特征)。
结果：本研究的总诊断率为33%（n=33例）。我们在WDR45、ARX、PCDH19,SCN1A,CACNA1A,LGI1、ASPM、MECP2、NF1、TSC2和CDK13。基因诊断率如下：发育迟缓/智力残疾的病例38.7％（24/62），无发育迟缓/智力残疾的病例23.6％（9/38）；脑畸形的病例46.8％（15/32），无脑畸形的病例25％（16/64）；大头/小头畸形的病例50％（6/12），无大/小头/小头畸形的病例28.4％（25/88）；
结论：基因型-表型相关性在癫痫等疾病中更为重要。其中包括许多基因和这些基因的变异。我们详细介绍了携带11个新变体的病例的临床发现，包括畸形特征，伴随神经发育障碍，脑电图结果,和脑部MRI结果。
