PDF(Pubmed)
Abstract：
UNASSIGNED: KCNQ2-related disorder is typically characterized as neonatal onset seizure and epileptic encephalopathy. The relationship between its phenotype and genotype is still elusive. This study aims to provide clinical features, management, and prognosis of patients with novel candidate variants of the KCNQ2 gene.
UNASSIGNED: We enrolled patients with novel variants in the KCNQ2 gene from the China Neonatal Genomes Project between January 2018 and January 2021. All patients underwent next-generation sequencing tests and genetic data were analyzed by an in-house pipeline. The pathogenicity of variants was classified according to the guideline of the American College of Medical Genetics. Each case was evaluated by two geneticists back to back. Patients\' information was acquired from clinical records.
UNASSIGNED: A total of 30 unrelated patients with novel variants in the KCNQ2 gene were identified, including 19 patients with single-nucleotide variants (SNVs) and 11 patients with copy number variants (CNVs). For the 19 SNVs, 12 missense variants and 7 truncating variants were identified. Of them, 36.8% (7/19) of the KCNQ2 variants were located in C-terminal regions, 15.7% (3/19) in segment S2, and 15.7% (3/19) in segment S4. Among them, 18 of 19 patients experienced seizures in the early neonatal period. However, one patient presented neurodevelopmental delay (NDD) as initial phenotype when he was 2 months old, and he had severe NDD when he was 3 years old. This patient did not present seizure but had abnormal electrographic background activity and brain imaging. Moreover, for the 11 patients with CNVs, 20q13.3 deletions involving EEF1A2, KCNQ2, and CHRNA4 genes were detected. All of them presented neonatal-onset seizures, responded to antiepileptic drugs, and had normal neurological development.
UNASSIGNED: In this study, patients with novel KCNQ2 variants have variable phenotypes, whereas patients with 20q13.3 deletion involving EEF1A2, KCNQ2, and CHRNA4 genes tend to have normal neurological development.
UNASSIGNED: We enrolled patients with novel variants in the KCNQ2 gene from the China Neonatal Genomes Project between January 2018 and January 2021. All patients underwent next-generation sequencing tests and genetic data were analyzed by an in-house pipeline. The pathogenicity of variants was classified according to the guideline of the American College of Medical Genetics. Each case was evaluated by two geneticists back to back. Patients\' information was acquired from clinical records.
UNASSIGNED: A total of 30 unrelated patients with novel variants in the KCNQ2 gene were identified, including 19 patients with single-nucleotide variants (SNVs) and 11 patients with copy number variants (CNVs). For the 19 SNVs, 12 missense variants and 7 truncating variants were identified. Of them, 36.8% (7/19) of the KCNQ2 variants were located in C-terminal regions, 15.7% (3/19) in segment S2, and 15.7% (3/19) in segment S4. Among them, 18 of 19 patients experienced seizures in the early neonatal period. However, one patient presented neurodevelopmental delay (NDD) as initial phenotype when he was 2 months old, and he had severe NDD when he was 3 years old. This patient did not present seizure but had abnormal electrographic background activity and brain imaging. Moreover, for the 11 patients with CNVs, 20q13.3 deletions involving EEF1A2, KCNQ2, and CHRNA4 genes were detected. All of them presented neonatal-onset seizures, responded to antiepileptic drugs, and had normal neurological development.
UNASSIGNED: In this study, patients with novel KCNQ2 variants have variable phenotypes, whereas patients with 20q13.3 deletion involving EEF1A2, KCNQ2, and CHRNA4 genes tend to have normal neurological development.
摘要：
未经证实：KCNQ2相关疾病的典型特征为新生儿发作性癫痫和癫痫性脑病。其表型和基因型之间的关系仍然难以捉摸。本研究旨在提供临床特征，管理,以及具有KCNQ2基因新候选变异体的患者的预后。
UNASSIGNED：我们在2018年1月至2021年1月期间从中国新生儿基因组项目招募了KCNQ2基因新变异的患者。所有患者都接受了下一代测序测试，并通过内部管道分析了遗传数据。根据美国医学遗传学学会的指南对变异体的致病性进行分类。每个病例都由两名遗传学家背靠背进行评估。患者信息来自临床记录。
UNASSIGNED：共鉴定出30例无关的患者在KCNQ2基因中有新的变异，包括19例单核苷酸变异（SNV）患者和11例拷贝数变异（CNV）患者。对于19个SNV，鉴定了12个错义变体和7个截短变体。其中,36.8%（7/19）的KCNQ2变体位于C端区域，S2段15.7%（3/19），S4段15.7%（3/19）。其中,19例患者中有18例在新生儿早期出现癫痫发作。然而,一名患者在2个月大时出现神经发育迟缓（NDD）作为初始表型，他3岁时患有严重的NDD。该患者没有出现癫痫发作，但有异常的电子照相背景活动和脑成像。此外，对于11名CNVs患者，检测到涉及EEF1A2、KCNQ2和CHRNA4基因的20q13.3缺失。他们都出现了新生儿发作的癫痫,对抗癫痫药物有反应，神经发育正常.
未经批准：在这项研究中，具有新型KCNQ2变体的患者具有可变的表型，而涉及EEF1A2,KCNQ2和CHRNA4基因的20q13.3缺失患者往往具有正常的神经发育.
UNASSIGNED：我们在2018年1月至2021年1月期间从中国新生儿基因组项目招募了KCNQ2基因新变异的患者。所有患者都接受了下一代测序测试，并通过内部管道分析了遗传数据。根据美国医学遗传学学会的指南对变异体的致病性进行分类。每个病例都由两名遗传学家背靠背进行评估。患者信息来自临床记录。
UNASSIGNED：共鉴定出30例无关的患者在KCNQ2基因中有新的变异，包括19例单核苷酸变异（SNV）患者和11例拷贝数变异（CNV）患者。对于19个SNV，鉴定了12个错义变体和7个截短变体。其中,36.8%（7/19）的KCNQ2变体位于C端区域，S2段15.7%（3/19），S4段15.7%（3/19）。其中,19例患者中有18例在新生儿早期出现癫痫发作。然而,一名患者在2个月大时出现神经发育迟缓（NDD）作为初始表型，他3岁时患有严重的NDD。该患者没有出现癫痫发作，但有异常的电子照相背景活动和脑成像。此外，对于11名CNVs患者，检测到涉及EEF1A2、KCNQ2和CHRNA4基因的20q13.3缺失。他们都出现了新生儿发作的癫痫,对抗癫痫药物有反应，神经发育正常.
未经批准：在这项研究中，具有新型KCNQ2变体的患者具有可变的表型，而涉及EEF1A2,KCNQ2和CHRNA4基因的20q13.3缺失患者往往具有正常的神经发育.
