McLellan Ailsa, Phillips Hilary A, Rittey Christopher, Kirkpatrick Martin, Mulley John C, Goudie David, Stephenson John B P, Tolmie John, Scheffer Ingrid E, Berkovic Samuel F, Zuberi Sameer M
Ninewells Hospital and Medical School, Dundee, Scotland.
Epilepsia. 2003 Apr;44(4):613-7. doi: 10.1046/j.1528-1157.2003.20102.x.
Mutations in genes coding for the alpha 4 and beta 2 subunits of the neuronal nicotinic acetylcholine receptor receptor (CHRN) are known to cause autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Here we examined the phenotypes in two families, from the same ethnic and geographic backgrounds, with ADNFLE as a result of mutations in these two different subunits of CHRN.
All affected family members underwent a detailed clinical evaluation and review of available EEG, neuroimaging, and videotapes of seizures. The molecular study of family D is reported here; family S has a previously reported mutation in the beta 2 subunit of CHRN.
A total of 16 individuals with ADNFLE were identified in the two families. In both families, seizure semiology, age at seizure onset, and the natural history of the seizure disorder was similar. Intrafamilial variation in terms of severity of epilepsy syndrome was present in both families. A significant number of individuals from each family had a history of psychological problems. The molecular study of family D revealed a Ser248Phe mutation in the alpha 4 subunit of CHRN.
The epilepsy phenotype is not distinguishable in the two families who have ADNFLE as a result of mutations in genes coding for different CHRN subunits. This is likely to be due to the similar functional consequences of each mutation on the CHRN receptor.
已知编码神经元烟碱型乙酰胆碱受体（CHRN）α4和β2亚基的基因突变会导致常染色体显性遗传性夜间额叶癫痫（ADNFLE）。在此，我们研究了来自相同种族和地理背景的两个家族的表型，这两个家族因CHRN这两个不同亚基的突变而患有ADNFLE。
所有受影响的家族成员均接受了详细的临床评估，并对现有的脑电图、神经影像学和癫痫发作录像进行了回顾。本文报道了家族D的分子研究；家族S先前已报道在CHRN的β2亚基中有一个突变。
在这两个家族中总共鉴定出16名患有ADNFLE的个体。在两个家族中，癫痫发作症状学、癫痫发作起始年龄以及癫痫疾病的自然史均相似。两个家族中均存在癫痫综合征严重程度的家族内差异。每个家族中有相当数量的个体有心理问题史。家族D的分子研究揭示了CHRNα4亚基中的Ser248Phe突变。
在因编码不同CHRN亚基的基因突变而患有ADNFLE的两个家族中，癫痫表型无法区分。这可能是由于每个突变对CHRN受体具有相似的功能影响。
