PDF(Pubmed)
Abstract：
BACKGROUND: Dravet syndrome, a rare genetic disorder with early-onset epileptic encephalopathy, was first described by Dravet in 1978. Dravet syndrome is most frequently caused by various mutations of the SCN1A gene encoding the type 1 subunit of the neuronal voltage-gated sodium channel.
METHODS: Two sisters of a non-consanguineous Palestinian family from the Arab community in Israel attended our child development and pediatric neurology clinic due to recurrent seizures and developmental delay. Genomic DNA was extracted from peripheral blood lymphocytes of all family members and a SCN1A mutation in exon 10 was revealed by Sanger sequencing in both affected siblings but not in the parents. Our data present a case of Dravet syndrome caused by a novel heterozygous SCN1A deletion (c.1458_1465delCTCTAAGT) in two affected siblings. Our findings add to the spectrum of mutations known in the SCN1A gene and confirm parental mosaicism as a mechanism relevant for transmission of this disease.
CONCLUSIONS: These cases confirm parental mosaicism in the transmission of Dravet syndrome and add to the spectrum of known mutations of the SCN1A gene. Repeated reports on parental mosaicism should remind us that there is a risk of recurrence even if the mutation is apparently de novo.
METHODS: Two sisters of a non-consanguineous Palestinian family from the Arab community in Israel attended our child development and pediatric neurology clinic due to recurrent seizures and developmental delay. Genomic DNA was extracted from peripheral blood lymphocytes of all family members and a SCN1A mutation in exon 10 was revealed by Sanger sequencing in both affected siblings but not in the parents. Our data present a case of Dravet syndrome caused by a novel heterozygous SCN1A deletion (c.1458_1465delCTCTAAGT) in two affected siblings. Our findings add to the spectrum of mutations known in the SCN1A gene and confirm parental mosaicism as a mechanism relevant for transmission of this disease.
CONCLUSIONS: These cases confirm parental mosaicism in the transmission of Dravet syndrome and add to the spectrum of known mutations of the SCN1A gene. Repeated reports on parental mosaicism should remind us that there is a risk of recurrence even if the mutation is apparently de novo.
摘要：
背景：德拉韦综合征，一种罕见的遗传性早发性癫痫脑病,1978年由Dravet首次描述。Dravet综合征最常见的原因是编码神经元电压门控钠通道1型亚基的SCN1A基因的各种突变。
方法：由于反复发作和发育迟缓，来自以色列阿拉伯社区的一个非血缘关系的巴勒斯坦家庭的两个姐妹参加了我们的儿童发育和儿科神经科诊所。从所有家庭成员的外周血淋巴细胞中提取基因组DNA，通过Sanger测序在两个受影响的兄弟姐妹中发现了外显子10中的SCN1A突变，但在父母中却没有。我们的数据显示了一例由两个受影响的兄弟姐妹中的新型杂合SCN1A缺失（c.1458_1465delCTCTAAGT）引起的Dravet综合征。我们的发现增加了SCN1A基因中已知的突变谱，并证实了亲本镶嵌性是与该疾病传播相关的机制。
结论：这些病例证实了父母在Dravet综合征传播中的镶嵌性，并增加了SCN1A基因的已知突变谱。关于父母镶嵌的重复报道应该提醒我们，即使突变显然是从头突变，也有复发的风险。
方法：由于反复发作和发育迟缓，来自以色列阿拉伯社区的一个非血缘关系的巴勒斯坦家庭的两个姐妹参加了我们的儿童发育和儿科神经科诊所。从所有家庭成员的外周血淋巴细胞中提取基因组DNA，通过Sanger测序在两个受影响的兄弟姐妹中发现了外显子10中的SCN1A突变，但在父母中却没有。我们的数据显示了一例由两个受影响的兄弟姐妹中的新型杂合SCN1A缺失（c.1458_1465delCTCTAAGT）引起的Dravet综合征。我们的发现增加了SCN1A基因中已知的突变谱，并证实了亲本镶嵌性是与该疾病传播相关的机制。
结论：这些病例证实了父母在Dravet综合征传播中的镶嵌性，并增加了SCN1A基因的已知突变谱。关于父母镶嵌的重复报道应该提醒我们，即使突变显然是从头突变，也有复发的风险。
