本文選題：視網(wǎng)膜色素變性 + 基因　； 參考：《南昌大學(xué)》2017年碩士論文

【摘要】：背景:視網(wǎng)膜色素變性(retinitis pigmentosa,RP)是與視錐細(xì)胞和視桿細(xì)胞(光感受器)或色素上皮結(jié)構(gòu)或功能異常相關(guān)的一類(lèi)進(jìn)行性致盲性遺傳眼病。國(guó)外患病率約為1/4000,我國(guó)患病率約為1/3467。視網(wǎng)膜色素變性的典型臨床特征為:早期出現(xiàn)夜盲,隨著病情進(jìn)展逐漸出現(xiàn)進(jìn)行性視野縮小和視力下降、視盤(pán)蠟黃色萎縮、視網(wǎng)膜骨細(xì)胞樣色素沉著等。視網(wǎng)膜色素變性具有高度的遺傳異質(zhì)性,據(jù)其遺傳方式可分為常染色體顯性遺傳(autosomal dominant RP,adRP)、常染色體隱性遺傳、X-連鎖遺傳、雙基因型遺傳和線粒體DNA遺傳。常染色體顯性遺傳在視網(wǎng)膜色素變性患者中所占比例為15%-20%,目前已確定與adRP有關(guān)的基因約有14個(gè),包括CA4、CRX、GUCA1B、IMPDH1、NRL、PRPF8、PRPF3、PRPF31、RHO、RDS、ROM1、RP9、RP1、SEMA4A。NRL(neural retinal leucine zippe,神經(jīng)視網(wǎng)膜亮氨酸拉鏈基因)基因編碼堿性亮氨酸拉鏈蛋白(basic motif-leucine zipper,bZIP),其對(duì)光感受器特異性基因-視紫紅質(zhì)(rhodopsin,RHO)基因的表達(dá)起調(diào)控作用。目的:對(duì)一個(gè)視網(wǎng)膜色素變性家系進(jìn)行臨床特點(diǎn)分析和遺傳學(xué)分析,明確其致病突變及可能發(fā)病機(jī)制。方法:收集一視網(wǎng)膜色素變性家系的所有家系成員的臨床資料,對(duì)本家系的5例患者和數(shù)名正常家庭成員進(jìn)行全面的眼科檢查,各取外周血2ml,提取外周靜脈血細(xì)胞基因組DNA。應(yīng)用眼科RP候選基因芯片(共包含59個(gè)目標(biāo)基因),采用目標(biāo)區(qū)域捕獲二代測(cè)序?qū)ο茸C者進(jìn)行基因突變分析,應(yīng)用一代測(cè)序驗(yàn)證對(duì)家系成員突變位點(diǎn)情況驗(yàn)證,應(yīng)用UCSC在線及polyhpen-2對(duì)突變位點(diǎn)進(jìn)行生物信息學(xué)分析。結(jié)果:該家系中連續(xù)3代,所有患者均有典型的色素型視網(wǎng)膜色素變性表現(xiàn),臨床上表現(xiàn)為不同程度夜盲、周邊視野縮窄、中心視力下降,該家系遺傳學(xué)研究發(fā)現(xiàn)該病在家系中呈現(xiàn)常染色體顯性遺傳,該家系3例患者的RP候選基因遺傳分析結(jié)果顯示,NRL基因第號(hào)外顯子上中均發(fā)現(xiàn)單一雜合突變c.152CT,該家系其他正常成員均未發(fā)現(xiàn)此突變,與該家系涉及的疾病呈共分離的特點(diǎn)。在蛋白水平,此突變導(dǎo)致NRL基因51位上編碼氨基酸由脯氨酸變?yōu)榱涟彼帷＝Y(jié)論:我們對(duì)一個(gè)中國(guó)視網(wǎng)膜色素變性家系進(jìn)行了詳細(xì)的臨床檢查,該本研究中家系成員共3代,每一代均有視網(wǎng)膜色素變性患者,家系中患者均有夜盲、視力下降、視野縮窄的臨床表現(xiàn);對(duì)該家系進(jìn)行分子遺傳學(xué)分析,發(fā)現(xiàn)了導(dǎo)致該家系患者患病的致病性突變c.152CT(p.Pro51Leu),該突變導(dǎo)致bZIP蛋白第152位脯胺酸被亮氨酸取代,進(jìn)而影響蛋白質(zhì)的功能。
[Abstract]:Background: retinitis pigmentosa RP (RP) is a kind of progressive blindness hereditary ophthalmopathy associated with conus cells and rod cells (photoreceptors) or abnormal structure or function of pigment epithelium. The prevalence rate in foreign countries is about 1 / 4 000 and in China is about 1 / 3 467. The typical clinical features of retinitis pigmentosa are as follows: early night-blindness, progressive narrowing of visual field and visual acuity, wax-yellow atrophy of optic disc, retinal osteocytoid pigmentation and so on. Retinitis pigmentosa has a high degree of genetic heterogeneity. According to its genetic pattern, it can be divided into autosomal dominant inheritance (autosomal dominant), autosomal recessive inheritance (X-), double genotype inheritance and mitochondrial DNA inheritance. The proportion of autosomal dominant inheritance in retinitis pigmentosa patients is 15 to 20. At present, there are about 14 genes related to adRP that have been identified. These genes include CA4, CRXG, GUCA1B, IMPDH1, NRLN, PRPF8, PRPF3, PRPF31, RDS-ROM1, RP9, RP1, SEMA4A.NRL (neural retinal leucine zippe, encoding basic leucine zipper protein (basic motif-leucine zipperbZIP), which plays a regulatory role in the expression of the photoreceptor specific gene rhodopsin Rho (rhodopsin Rho) gene. Objective: to analyze the clinical and genetic characteristics of a pedigree with retinitis pigmentosa, and to identify the mutation and possible pathogenesis of retinitis pigmentosa. Methods: the clinical data of all the family members of a family with retinitis pigmentosa were collected, and 5 patients and several normal family members were examined by ophthalmology. The peripheral blood 2ml was taken and the genomic DNA of peripheral venous blood cells (DNA) was extracted. Using ophthalmic RP candidate gene chip (including 59 target genes), the gene mutation of the proband was analyzed by target region capture second generation sequencing, and the mutation loci of the family members were verified by the first generation sequencing. UCSC and polyhpen-2 were used for bioinformatics analysis of mutation sites. Results: all the patients had typical pigmented retinitis pigmentosa. The clinical manifestations were night blindness, peripheral visual field constriction and central visual acuity decline. The pedigree genetic study found that autosomal dominant inheritance was present in the homelands. Genetic analysis of RP candidate genes in 3 patients in this family showed that a single heterozygous mutation c.152CTwas found in exon number 1 of the NRL gene, but no mutation was found in other normal members of the family, which was coisolated from the disease involved in the family. At the protein level, the mutation resulted in the conversion of amino acids from proline to leucine at position 51 of the NRL gene. Conclusion: a Chinese pedigree with retinitis pigmentosa was examined in detail. In this study, there were 3 generations of family members, each generation of patients with retinal pigmentosa, all the patients in the family had night blindness, visual acuity was decreased. The clinical manifestation of visual field constriction, molecular genetic analysis of the family, found the pathogenicity mutation c.152CT (p.Pro51Leu), which caused the 152nd proline of bZIP protein to be replaced by leucine, and then affected the function of protein.
【學(xué)位授予單位】：南昌大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R774.1

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 閆光輝;盛迅?jìng)?;中國(guó)視網(wǎng)膜色素變性相關(guān)基因研究現(xiàn)狀[J];中華眼底病雜志;2011年05期

2 江江;孫安;李壽玲;汪淵;高敏;龔健楊;周青;王再興;杜文輝;;X-性連鎖隱性遺傳視網(wǎng)膜色素變性致病基因的突變檢測(cè)[J];安徽醫(yī)科大學(xué)學(xué)報(bào);2010年01期

3 張馨方;盛迅?jìng)?;視網(wǎng)膜色素變性的相關(guān)基因研究進(jìn)展[J];國(guó)際眼科雜志;2006年03期

4 莊文娟,盛迅?jìng)?常染色體顯性遺傳視網(wǎng)膜色素變性的相關(guān)基因研究概況[J];國(guó)際眼科雜志;2004年05期

5 鄧新國(guó),張清炯,肖學(xué)珊,黎仕強(qiáng),郭向明,賈小云,申煌煊;常染色體顯性視網(wǎng)膜色素變性NRL基因的突變研究[J];眼科研究;2003年02期

6 楊曉慧,孫葆忱;視網(wǎng)膜色素變性與基因突變[J];眼視光學(xué)雜志;2002年04期

7 張曉莉,楊冠寅,彭智培,府偉靈;視網(wǎng)膜色素變性患者中視網(wǎng)膜色素變性1基因點(diǎn)突變的研究[J];中華醫(yī)學(xué)遺傳學(xué)雜志;2002年03期

8 楊樺,羅成仁,周久模,嚴(yán)密,陳大年,黃倩;原發(fā)性視網(wǎng)膜色素變性家系的RDS基因Pro216 Leu突變及其表型研究[J];中華眼科雜志;2000年01期

9 張豐生,張清炯,申煌煊,黎仕強(qiáng),肖學(xué)珊;視網(wǎng)膜色素變性中視紫紅質(zhì)與Peripherin/RDS基因的突變篩查[J];眼科學(xué)報(bào);1998年04期

10 閆光輝;盛迅?jìng)?李自立;容維寧;李慧平;劉雅妮;馬潤(rùn)清;馬莉;;110例視網(wǎng)膜色素變性患者RP1基因突變的檢測(cè)分析[J];中華實(shí)驗(yàn)眼科雜志;2011年11期

，

本文編號(hào)：2111253