目的:研究视锥杆细胞同源盒基因(CRX)在宁夏地区视网膜色素变性(rentinitis pigmentosa,RP)患者中的突变频率及特征,并进一步探讨其在RP发病机制中潜在的机制。方法:运用聚合酶链反应(PCR)和直接测序方法,对100例RP患者(包括18例ADRP患者,15例ARRP患者,67例SRP患者)进行了CRX基因全编码区序列突变的检测,运用多因素分析研究CRX基因突变位点对RP的作用。结果:在100例RP患者CRX基因上共检测出5个变异位点,其中p.Leu78Leu,p.Ala92Ala和p.Thr187Ile为新发现的突变。其余位点突变均证实为CRX基因的多态性。p.Thr187Ile突变位点仅在2例ARRP患者身上检出,在正常对照组未发现该位点突变。结论:宁夏地区RP患者中,CRX基因的突变率低于其他人群中(小于1%)。p.Thr187Ile不是RP的致病性突变,但它是否可能通过影响其它基因的表达,增加常染色体显性遗传视网膜色素变性(ARRP)的发生,有待于进一步研究。

AIM:To identify the mutations of cone-rod homeobox gene(CRX) in the patients with retinitis pigmentosa(RP) in Ningxia and to evaluate their potential interaction in the pathogenesis of RP.METHODS:One hundred individuals with RP were recruited for this study from October 2009 to November 2010.Polymerase chain reaction(PCR) and direct DNA sequencing were used to screen in the entire coding region and splice sites of CRX gene.Multiple analysis was used to examine the role of CRX gene mutation on RP.RESULTS:In total 5 sequence variants gene were identified,2 synonymous variants(p.Leu78Leu and p.Ala92Ala),3 missense variants(p.Ala112Val,p.Gly122Asp and p.Thr187Ile).p.Ala112Val,p.Gly122Asp were reported as Single Nucleotide Polymorphisms(SNP) and showed no positive correlation with the RP confirmed by the multivariate logistic regression.The p.Thr187Ile variant was found in two ARRP(autosomal recessive RP) patients and was absent in normal control individuals.CONCLUSION:The prevalence of CRX mutation in Ningxia population(<1%) is lower than other populations.p.Thr187Ile was not a disease-causing mutation,but further study should be conducted to determine whether the p.Thr187Ile variant can effect the express of other gene and increase the risk of developing ARRP.

R774.1

中国宁夏回族自治区科技攻关基金资助项目(No.NKJ2009-232)~~