Gambardella A, Annesi G, De Fusco M, Patrignani A, Aguglia U, Annesi F, Pasqua A A, Spadafora P, Oliveri R L, Valentino P, Zappia M, Ballabio A, Casari G, Quattrone A
Institute of Neurology, School of Medicine, Catanzaro, Italy.
Neurology. 2000 Nov 28;55(10):1467-71. doi: 10.1212/wnl.55.10.1467.
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is caused by mutations in the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4) gene, mapping on chromosome 20q13.2. A second ADNFLE locus was mapped on chromosome 15q24.
To report a new third ADNFLE locus on chromosome 1 in a large Italian family.
The authors performed a clinical and genetic study in a large, three-generation ADNFLE family from southern Italy, including eight affected individuals and three obligate carriers.
The age at onset of seizures was around 9 years of age and all affected individuals manifested nocturnal partial seizures of frontal lobe origin. Interictal awake and sleep EEG recordings showed no definite epileptiform abnormalities in most patients. Ictal video-EEG showed that the attacks were partial seizures with a frontal lobe semiology. Intellectual and neurologic examinations, and brain CT or MRI results were always normal. Carbamazepine was effective in all treated patients. Exclusion mapping of the known loci linked to ADNFLE-ENFL1, and ENFL2, on chromosomes 20q13.2 and 15q24-was performed on the pedigree before starting the genome-wide linkage analysis. The whole genome scan mapping allowed the identification of a new ADNFLE locus spanning the pericentromeric region of chromosome 1.
The authors provided evidence for a third locus associated to autosomal dominant nocturnal frontal lobe epilepsy on chromosome 1. Among the known genes mapping within this critical region, the ss2 subunit of the nicotinic receptor (CHRNB2) represents the most obvious candidate.
常染色体显性遗传性夜间额叶癫痫（ADNFLE）由神经元烟碱型乙酰胆碱受体（CHRNA4）基因的α4亚基突变引起，该基因定位于20号染色体长臂1区3带2亚带（20q13.2）。第二个ADNFLE基因座定位于15号染色体长臂2区4带（15q24）。
报告一个意大利大家庭中位于1号染色体上的新的第三个ADNFLE基因座。
作者对一个来自意大利南部的大型三代ADNFLE家系进行了临床和遗传学研究，该家系包括8名受累个体和3名肯定携带者。
癫痫发作起始年龄约为9岁，所有受累个体均表现为起源于额叶的夜间部分性发作。大多数患者发作间期清醒和睡眠脑电图记录未显示明确的癫痫样异常。发作期录像脑电图显示发作均为具有额叶发作症状学的部分性发作（额叶癫痫发作）。智力和神经学检查以及脑部CT或MRI结果均正常。卡马西平对所有接受治疗的患者均有效。在开始全基因组连锁分析之前，先对该家系进行排除定位，排除与ADNFLE相关的已知基因座ENFL1和ENFL2，它们分别位于20号染色体长臂1区3带2亚带（20q13.2）和15号染色体长臂2区4带（15q24）。全基因组扫描定位发现了一个新的ADNFLE基因座，跨越1号染色体的着丝粒周围区域。
作者提供了证据，证明1号染色体上存在与常染色体显性遗传性夜间额叶癫痫相关的第三个基因座。在这个关键区域内已知的基因中，烟碱受体的β2亚基（CHRNB2）是最明显的候选基因。
