Abstract：
BACKGROUND: We aimed to delineate the genotype and phenotype of patients with KCNQ2 mutations from South China.
METHODS: Clinical manifestations and characteristics of KCNQ2 mutations of patients from South China were analyzed. Previous patients with mutations detected in this study were reviewed.
RESULTS: Eighteen epilepsy patients with KCNQ2 mutations, including seven self-limited neonatal epilepsy (SeLNE), two self-limited infantile epilepsy (SeLIE) and nine developmental and epileptic encephalopathy (DEE) were enrolled. The age of onset (p=0.006), mutation types (p=0.029), hypertonia (p=0.000), and seizure offset (p=0.029) were different in self-limited epilepsy (SeLE) and DEE. De novo mutations were mainly detected in DEE patients (p=0.026). The mutation position, EEG or the age of onset were not predictive for the seizure or ID/DD outcome in DEE, while the development of patients free of seizures was better than that of patients with seizures (p=0.008). Sodium channel blockers were the most effective anti-seizure medication, while the age of starting sodium channel blockers did not affect the seizure or development offset. We first discovered the seizure recurrence ratio in SeLNE/SeLIE was 23.1% in South China. Four novel mutations (c.790T>C, c.355_363delGAGAAGAG, c.296+2T>G, 20q13.33del) were discovered. Each of eight mutations (c.1918delC, c.1678C>T, c.683A>G, c.833T>C, c.868G>A, c.638G>A, c.997C>T, c.830C>T) only resulted in SeLE or DEE, while heterogeneity was also found. Six patients in this study have enriched the known phenotype caused by the mutations (c.365C>T, c.1A>G, c.683A>G, c.833T>C, c.830C>T, c.1678C>T).
CONCLUSIONS: This research has expanded known phenotype and genotype of KCNQ2-related epilepsy, and the different clinical features of SeLE and DEE from South China.
METHODS: Clinical manifestations and characteristics of KCNQ2 mutations of patients from South China were analyzed. Previous patients with mutations detected in this study were reviewed.
RESULTS: Eighteen epilepsy patients with KCNQ2 mutations, including seven self-limited neonatal epilepsy (SeLNE), two self-limited infantile epilepsy (SeLIE) and nine developmental and epileptic encephalopathy (DEE) were enrolled. The age of onset (p=0.006), mutation types (p=0.029), hypertonia (p=0.000), and seizure offset (p=0.029) were different in self-limited epilepsy (SeLE) and DEE. De novo mutations were mainly detected in DEE patients (p=0.026). The mutation position, EEG or the age of onset were not predictive for the seizure or ID/DD outcome in DEE, while the development of patients free of seizures was better than that of patients with seizures (p=0.008). Sodium channel blockers were the most effective anti-seizure medication, while the age of starting sodium channel blockers did not affect the seizure or development offset. We first discovered the seizure recurrence ratio in SeLNE/SeLIE was 23.1% in South China. Four novel mutations (c.790T>C, c.355_363delGAGAAGAG, c.296+2T>G, 20q13.33del) were discovered. Each of eight mutations (c.1918delC, c.1678C>T, c.683A>G, c.833T>C, c.868G>A, c.638G>A, c.997C>T, c.830C>T) only resulted in SeLE or DEE, while heterogeneity was also found. Six patients in this study have enriched the known phenotype caused by the mutations (c.365C>T, c.1A>G, c.683A>G, c.833T>C, c.830C>T, c.1678C>T).
CONCLUSIONS: This research has expanded known phenotype and genotype of KCNQ2-related epilepsy, and the different clinical features of SeLE and DEE from South China.
摘要：
背景：我们旨在描述中国南方KCNQ2突变患者的基因型和表型。
方法：分析华南地区KCNQ2基因突变患者的临床表现和特点。回顾了在本研究中检测到的突变的先前患者。
结果：18例具有KCNQ2突变的癫痫患者，包括七例自限性新生儿癫痫（SeLNE），纳入2例自限性婴儿癫痫(SeLIE)和9例发育性和癫痫性脑病(DEE).发病年龄（p=0.006），突变类型（p=0.029），高张力（p=0.000），自限性癫痫（SeLE）和DEE的癫痫发作偏移（p=0.029）不同。从头突变主要在DEE患者中检测到(p=0.026)。突变的位置，EEG或发病年龄不能预测DEE的癫痫发作或ID/DD结果，而无癫痫患者的发展优于癫痫患者（p=0.008）。钠通道阻滞剂是最有效的抗癫痫药物，而开始使用钠通道阻滞剂的年龄并不影响癫痫发作或发展偏移。我们首次发现中国南方的SeLNE/SeLIE癫痫复发率为23.1％。四个新突变（c.790T>C，c.355_363delGAGAAGAG，c.296+2T>G，20q13.33del）被发现。八个突变中的每一个(c.1918delC，c.1678C>T，c.683A>G，c.833T>C，c.868G>A，c.638G>A，c.997C>T，c.830C>T)仅导致SeLE或DEE，同时也发现了异质性。本研究中有6名患者丰富了由突变引起的已知表型（c.365C>T，c.1A>G，c.683A>G，c.833T>C，c.830C>T，c.1678C>T）。
结论：这项研究扩大了已知的KCNQ2相关癫痫的表型和基因型，以及中国南方地区SeLE和DEE的不同临床特征。
方法：分析华南地区KCNQ2基因突变患者的临床表现和特点。回顾了在本研究中检测到的突变的先前患者。
结果：18例具有KCNQ2突变的癫痫患者，包括七例自限性新生儿癫痫（SeLNE），纳入2例自限性婴儿癫痫(SeLIE)和9例发育性和癫痫性脑病(DEE).发病年龄（p=0.006），突变类型（p=0.029），高张力（p=0.000），自限性癫痫（SeLE）和DEE的癫痫发作偏移（p=0.029）不同。从头突变主要在DEE患者中检测到(p=0.026)。突变的位置，EEG或发病年龄不能预测DEE的癫痫发作或ID/DD结果，而无癫痫患者的发展优于癫痫患者（p=0.008）。钠通道阻滞剂是最有效的抗癫痫药物，而开始使用钠通道阻滞剂的年龄并不影响癫痫发作或发展偏移。我们首次发现中国南方的SeLNE/SeLIE癫痫复发率为23.1％。四个新突变（c.790T>C，c.355_363delGAGAAGAG，c.296+2T>G，20q13.33del）被发现。八个突变中的每一个(c.1918delC，c.1678C>T，c.683A>G，c.833T>C，c.868G>A，c.638G>A，c.997C>T，c.830C>T)仅导致SeLE或DEE，同时也发现了异质性。本研究中有6名患者丰富了由突变引起的已知表型（c.365C>T，c.1A>G，c.683A>G，c.833T>C，c.830C>T，c.1678C>T）。
结论：这项研究扩大了已知的KCNQ2相关癫痫的表型和基因型，以及中国南方地区SeLE和DEE的不同临床特征。
