一常染色体显性遗传视网膜色素变性家系的基因定位及临床表型与基因型关系的研究

发布时间：2018-03-20 18:15

本文选题：常染色体显性视网膜色素变性　切入点：视紫红质基因　出处：《安徽医科大学》2010年硕士论文　论文类型：学位论文

【摘要】： 目的(1)对一个RHO基因突变的中国人常染色体显性遗传视网膜色素变性(autosomal dominant RP, adRP)家系进行基因定位和突变研究(2)研究其临床表型特征和分析该家系基因突变与临床表型的关系。方法(1)收集一大的常染色体显性遗传的视网膜色素变性的家系,在获得知情同意的前提下对该家系的RP患者进行了病史采集,视力,视野,眼底检查,部分患者行视网膜电流图(ERG),眼底荧光血管造影(FFA),光学相干断层成像(OCT)检查。(2)抽取家系成员外周静脉血并提取DNA,并对该家系进行ADRP候选基因定位和定位区域候选基因突变检测。结果(1)该视网膜色素变性家系共5代,有32名成员,其中男性16例,女性16例,患者共12例,其中男性患者6例,女性6例,符合常染色体显现性遗传模式。家系的临床特点为发病早,病情发展迅速,病情较严重。患者1-2岁左右即被发现有夜盲,这是目前报道的RP家系中夜盲发生最早的病例。患者表现进行性的眼底骨细胞样色素沉着,视野缩小,ERG显示a,b波幅明显下降甚至熄灭,50岁左右失明;(2)通过对已知ADRP候选基因的连锁分析,结果提示该家系候选基因定位于第3号染色体RHO基因区域; RHO基因序列分析显示第2外显子编码区第512个碱基出现突变(512CT,p.P171L)。结论(1)视紫红质基因突变(P171L)是该常染色体视网膜色素变性家系的致病基因。(2)该常染色体视网膜色素变性家系的视紫红质基因突变(P171L)导致了严重的临床表型。
[Abstract]:Objective 1) to study the clinical phenotypic characteristics of a Chinese autosomal dominant retinitis pigmentosa (dominant) family with RHO gene mutation and to analyze the relationship between the gene mutation and the clinical phenotype. Methods A large pedigree with autosomal dominant retinitis pigmentosa was collected, and the history of history, visual acuity, visual field, and fundus examination of RP patients were examined with informed consent. Some of the patients were examined with ERG, fundus fluorescein angiography (FFAA) and optical coherence tomography (Oct). The peripheral venous blood of the family members was extracted and the DNA was extracted. The candidate gene location of ADRP and the mutation of candidate gene in the location region were detected. Results 1) there were 32 members in this family, including 16 males, 16 females and 12 patients, including 6 males and 6 females. The clinical characteristics of the family were early onset, rapid development of the disease, and the severity of the disease. The patient was found to have night blindness around 1-2 years of age. This is the earliest reported case of nocturnal blindness in RP pedigree. Visual field reduced ERG showed that the amplitude of AGB wave was significantly decreased or even extinguished by linkage analysis of known ADRP candidate genes. The results suggested that the candidate gene was located in the RHO gene region of chromosome 3, and the RHO gene sequence analysis showed the mutation of 512CTP. P171L in the coding region of exon 2. Conclusion (P 171L) is the pathogenic gene of retinitis pigmentosa in this autosomal retinitis pigmentosa pedigree (P 171L).
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R774.1

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