视网膜色素变性患者特异性光感受器细胞核受体基因突变检测分析

目的 观察特异性光感受器细胞核受体(NR2E3)基因在宁夏地区视网膜色素变性(RP)患者中的突变频率及特征，探讨其在RP发病机制中的作用。方法 经检查确诊的120例RP患者纳入研究。其中，常染色体显性遗传RP (ADRP)患者33例，来自18个家系；常染色体隐性遗传RP (ARRP)患者20例，来自15个家系；散发型RP(SRP)患者67例。选取100名健康成年人作为对照组。采用聚合酶链反应(PCR)和直接测序方法，检测NR2E3基因全编码区和邻近剪切位点的内含子区域序列突变。多因素分析研究NR2E3基因突变位点对RP的作用。结果 120例RP患者NR2E3基因检测出变异位点12个。其中，非编码区5个；第4、6、7外显子上7个。12个变异位点中，新发现变异位点6个。外显子上7个变异位点中，同义突变3个；错义突变4个。统计学分析结果显示，所有变异位点均为NR2E3基因多态性。多因素Logistic回归分析显示，变异位点均与RP发生无相关性。18例ADRP先证者、67例SRP患者和正常对照组中，分别有1、3、2例NR2E3基因第4外显子上发现p.Glu121Lys变异。发生该位点变异的ADRP患者家系（NXRP-1）另外8例患者中，出现p.Glu121Lys位点变异5例，未出现变异3例。出现变异的6例患者发病年龄较未出现p.Glu121Lys位点变异的3例患者早，且较早出现明显的中心视力损害。结论 宁夏地区RP患者NR2E3基因致病突变率小于1％，NR2E3基因的p.Glu121Lys变异发生率较低。

Mutations analysis of NR2E3 gene in Chinese patients with retinitis pigmentosa

Objective To screen and analyze NR2E3 gene mutations in rentinitis pigmentosa (RP)patients from Ningxia area of China. Method 120 RP patients were enrolled in this study. The patients include 33 autosomal dominant RP (ADRP) patients from 18 families, 20 autosomal recessive RP (ARRP)patients from 15 families, and 67 simplex RP (SRP) patients. 100 healthy people were collected as the control group. PCR and direct DNA sequencing were used to screen the entire coding region and splice sites of NR2E3 gene. Multiple analysis was used to study the effects of NR2E3 gene on RP. Results A total of 12 different sequence variants in the NR2E3 gene were identified, including 6 novel sequence variants. 5variants were detected in non-coding regions; 7 variants were detected on the 4th, 6th, 7th exon which including 3 synonymous mutations and 4 missense mutations. All of them were NR2E3 gene polymorphisms and showed no positive correlation with the RP confirmed by the multivariate logistic regression analysis.The missense mutation of p. Glu121Lys was first found in 1 ADRP proband, 2 SRP patients and 2 control subjects. Among other 8 affected individuals in this ADRP family, 5 patients also had the p. Glu121Lys variant. Notably, the 6 affected individuals with p. Glu121Lys showed more serious ophthalmic findings (early onset and early central visual impairment) than other 3 affected individuals without p. Glu121Lys.Conclusion The mutation frequency of NR2E3 and p. Glu121Lys variant in NR2E3 gene in Ningxia RP patients were lower than previous reports in other populations.