Human Genetics文章：兒童失神性癲癇患者NIPA2基因存在突變
盡管染色體15q11.2區拷貝數變異已經被確認可以引起高加索人群特發性全身性癲癇(idiopathic generalized epilepsy, IGE)，不過該區域存在的癲癇基因尚不清楚。研究中檢測了中國兒童失神性癲癇（childhood absence epilepsy，CAE）人群15q11.2區拷貝數變異，并檢測該區域的選擇性鎂離子轉運蛋白基因NIPA2的微缺失是否是引起CAE的易感基因。研究者使用Affymetrix SNP5.0芯片檢測了來自中國北方得到198位CAE患者和198個對照中的IGE相關的拷貝數變異情況，并通過基于高密度芯片的比較基因組雜交進行確認。進而對全部380例CAE患者和400例對照樣品的NIPA2基因編碼區和外顯子-內含子邊界區域進行了測序。在198個CAE病人中發現3例(1.5%)存在15q11.2區微缺失而在對照組沒有檢測到缺失情況。在380例患者中有3例檢測到了處于雜合狀態的NIPA2基因存在點突變或插入/缺失，在700例對照中則不存在這些突變形式(P=0.043)。這些突變形式包括2種新發的錯義突變(c.532A>T, p.I178F; c.731A>G, p.N244S )，和一種新發的小片段插入(c.1002_1003insGAT, p.N334_335EinsD )，這些突變形式在400例對照樣品中均沒有檢測到。在本研究第一次鑒定了選擇性鎂離子結合蛋白基因NIPA2是兒童失神性癲癇的易感基因，確定微缺失是染色體15q11.2區拷貝數變異重要的疾病形式，這些突變在中國的疾病人群中具有比已報道的高加索人群更高的發生頻率。NIPA2基因的單倍劑量不足可能是15q11.2區微缺失造成神經系統表現的機制之一。
上述研究中，Affymetrix SNP 5.0芯片服務在博奧生物有限公司完成。
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.