本文選題：視網(wǎng)膜色素變性 + NR2E3基因��； 參考：《寧夏醫(yī)科大學》2012年碩士論文

【摘要】：目的視網(wǎng)膜色素變性(RP)是一種常見的致盲性遺傳眼病，目前已發(fā)現(xiàn)至少62個基因與其有關(guān)，并且每個突變基因?qū)煌倪z傳類型的RP患者。本研究目的觀察特異性光感受器細胞核受體（NR2E3）基因在寧夏地區(qū)RP患者中的突變頻率及特征，并探討其在RP發(fā)病機制中的作用。 方法經(jīng)全面眼科檢查確診的120例RP患者納入研究。研究對象均來自寧夏回族自治區(qū)，其中，常染色體顯性遺傳RP（adRP）患者33例，來自18個家系；常染色體隱性遺傳RP（arRP）患者20例，來自15個家系；散發(fā)型RP（sRP）患者67例。同時選取100名健康成年人作為對照組。抽取受檢者外周靜脈血3～5ml，乙二胺四乙酸（EDTA）抗凝，采用北京天根公司的DNA抽提試劑盒提取全基因組DNA，按已發(fā)表的NR2E3基因序列資料（GeneBank accession No.：NG_009113），參照Yang等報道設(shè)計引物，運用聚合酶鏈反應（PCR）和直接測序方法，進行NR2E3基因全編碼區(qū)和鄰近剪切位點的內(nèi)含子區(qū)域序列突變的檢測，再運用多因素logistic分析研究NR2E3基因突變位點對RP的作用。 結(jié)果120例RP患者NR2E3基因檢測出變異位點12個；其中，，5個位于非編碼區(qū)，7個位于第4、6、7外顯子上。12個變異位點中，新發(fā)現(xiàn)變異位點6個。外顯子上7個變異位點中，同義突變3個；錯義突變4個。統(tǒng)計學分析結(jié)果顯示，所有變異位點均為NR2E3基因多態(tài)性。多因素Logistic回歸分析顯示，變異位點均與RP的發(fā)生無相關(guān)性。18例adRP先證者、67例sRP患者和正常對照組中，分別有1、3、2例先證者的NR2E3基因第4外顯子上發(fā)現(xiàn)p.Glu121Lys變異。發(fā)生該位點變異的adRP患者家系（NXRP-1）另外8例患者中，出現(xiàn)p.Glu121Lys位點變異5例，未出現(xiàn)變異3例。出現(xiàn)變異的6例患者發(fā)病年齡較未出現(xiàn)p.Glu121Lys位點變異的3例患者早，且較早出現(xiàn)明顯的中心視力損害。 結(jié)論寧夏地區(qū)RP患者NR2E3基因致病突變率小于1%，明顯低于中國其他地區(qū)的報道。一個adRP家系（NXRP-1）NR2E3基因中p.Glu121Lys變異與RP未出現(xiàn)“共分離”現(xiàn)象，因此p.Glu121Lys不是導致該家系發(fā)生RP的致病原因，但此位點多態(tài)性在該家系9例患者中發(fā)現(xiàn)6例，其臨床表型較未出現(xiàn)p.Glu121Lys位點多態(tài)性的RP患者嚴重，可能系修飾基因。
[Abstract]:Objective retinitis pigmentosa (RP) is a common blindness hereditary ophthalmopathy. At least 62 genes have been found to be associated with RP, and each mutant gene corresponds to a different genetic type of RP patients. Objective to observe the mutation frequency and characteristics of specific photoreceptor nuclear receptor (NR2E3) gene in RP patients in Ningxia and to explore its role in the pathogenesis of RP. Methods 120 RP patients confirmed by ophthalmology were included in the study. The subjects were 33 autosomal dominant RP (ADRP) patients from 18 families, 20 autosomal recessive RP (ARRP) patients from 15 families, and 67 sporadic RP (SRP) patients. At the same time, 100 healthy adults were selected as control group. The peripheral venous blood (3ml) and ethylenediamine tetraacetic acid (EDTA) were extracted from the peripheral venous blood of the subjects. The whole genome DNA was extracted by using the DNA extraction kit of Beijing Tiangen Company. According to the published data of NR2E3 gene sequence (GeneBank accession No.: NG009113), the primers were designed with reference to Yang et al. Polymerase chain reaction (PCR) and direct sequencing were used to detect the mutations in the intron region of NR2E3 gene, and the effect of NR2E3 mutation site on RP was studied by multivariate logistic analysis. Results there were 12 NR2E3 mutation loci in 120 patients with RP, of which 5 were located in non-coding region and 7 in exon 4, 6 of which were newly discovered. Of the 7 mutation sites in exon, 3 were synonymous mutations and 4 were missense mutations. Statistical analysis showed that all mutation sites were NR2E3 gene polymorphisms. Multivariate logistic regression analysis showed that there was no correlation between the mutation sites and the occurrence of RP. In the 18 cases of adRP probands, 67 cases of SRP patients and 2 cases of normal controls, the mutation of P. Glu121Lys was found in exon 4 of NR2E3 gene in 2 cases of proband. Among the other 8 patients with NXRP-1, 5 had the mutation of p.Glu121Lys, and 3 had no variation. The onset age of 6 patients with mutation was earlier than that of 3 patients without the mutation of p.Glu121Lys, and the central visual impairment was earlier than that of the patients without the mutation of p.Glu121Lys. Conclusion the mutation rate of NR2E3 gene in RP patients in Ningxia is less than 1, which is significantly lower than that reported in other regions of China. In an adRP pedigree (NXRP-1) NR2E3 gene, p Glu121Lys mutation was not cosegregated with RP, so P. Glu121Lys was not the cause of RP in this pedigree, but this locus polymorphism was found in 6 out of 9 patients in this pedigree. Its clinical phenotype is more serious than that of RP patients without P. Glu121 Lys polymorphism, and it may be a modified gene.
【學位授予單位】：寧夏醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R774.1

【參考文獻】

相關(guān)期刊論文 前1條

1 容維寧;盛迅倫;莊文娟;;常染色體顯性遺傳視網(wǎng)膜色素變性家系視紫紅質(zhì)基因突變分析[J];國際眼科雜志;2006年05期

本文編號：2081182