Human Genetics文章：儿童失神性癫痫患者NIPA2基因存在突变
尽管染色体15q11.2区拷贝数变异已经被确认可以引起高加索人群特发性全身性癫痫(idiopathic generalized epilepsy, IGE)，不过该区域存在的癫痫基因尚不清楚。研究中检测了中国儿童失神性癫痫（childhood absence epilepsy，CAE）人群15q11.2区拷贝数变异，并检测该区域的选择性镁离子转运蛋白基因NIPA2的微缺失是否是引起CAE的易感基因。研究者使用Affymetrix SNP5.0芯片检测了来自中国北方得到198位CAE患者和198个对照中的IGE相关的拷贝数变异情况，并通过基于高密度芯片的比较基因组杂交进行确认。进而对全部380例CAE患者和400例对照样品的NIPA2基因编码区和外显子-内含子边界区域进行了测序。在198个CAE病人中发现3例(1.5%)存在15q11.2区微缺失而在对照组没有检测到缺失情况。在380例患者中有3例检测到了处于杂合状态的NIPA2基因存在点突变或插入/缺失，在700例对照中则不存在这些突变形式(P=0.043)。这些突变形式包括2种新发的错义突变(c.532A>T, p.I178F; c.731A>G, p.N244S )，和一种新发的小片段插入(c.1002_1003insGAT, p.N334_335EinsD )，这些突变形式在400例对照样品中均没有检测到。在本研究第一次鉴定了选择性镁离子结合蛋白基因NIPA2是儿童失神性癫痫的易感基因，确定微缺失是染色体15q11.2区拷贝数变异重要的疾病形式，这些突变在中国的疾病人群中具有比已报道的高加索人群更高的发生频率。NIPA2基因的单倍剂量不足可能是15q11.2区微缺失造成神经系统表现的机制之一。
上述研究中，Affymetrix SNP 5.0芯片服务在博奥生物有限公司完成。
原文摘要：
NIPA2 located in 15q11.2 is mutated in patients with childhood absence epilepsy
While pathogenic copy number variations (CNVs) in 15q11.2 were recently identified in Caucasian patients with idiopathic generalized epilepsies (IGEs), the epilepsy-associated gene(s) in this region is/are still unknown. Our study investigated whether the CNVs in 15q11.2 are associated with childhood absence epilepsy (CAE) in Chinese patients and whether the selective magnesium transporter NIPA2 gene affected by 15q11.2 microdeletions is a susceptive gene for CAE. We assessed IGE-related CNVs by Affymetrix SNP 5.0 microarrays in 198 patients with CAE and 198 controls from northern China, and verified the identified CNVs by high-density oligonucleotide-based CGH microarrays. The coding region and exon–intron boundaries of NIPA2 were sequenced in all 380 patients with CAE and 400 controls. 15q11.2 microdeletions were detected in 3 of 198 (1.5%) patients and in no controls. Furthermore, we identified point mutations or indel in a heterozygous state of the NIPA2 gene in 3 out of 380 patients, whereas they were absent in 700 controls (P = 0.043). These mutations included two novel missense mutations (c.532A>T, p.I178F; c.731A>G, p.N244S) and one small novel insertion (c.1002_1003insGAT, p.N334_335EinsD). No NIPA2 mutation was found in 400 normal controls. We first identified that NIPA2, encoding a selective magnesium transporter, is a susceptible gene of CAE, and 15q11.2 microdeletions are important pathogenic CNVs for CAE with higher frequency in Chinese populations than that previously reported in Caucasians. The haploinsufficiency of NIPA2 may be a mechanism underlying the neurological phenotypes of 15q11.2 microdeletions.