江西籍原发性开角型青光眼家系的遗传学调查及与WDR36基因突变的相关性研究

发布时间：2018-02-08 17:57

  本文关键词： 家族性原发性开角型青光眼 遗传方式 WDR36基因 基因突变　出处：《南昌大学》2010年硕士论文　论文类型：学位论文

【摘要】： 目的:研究一个江西籍原发性开角型青光眼家系的临床及遗传学特点;检测该家系成员是否存在WDR36基因突变,探讨WDR36基因在该POAG家系发病中可能的作用。 方法:经我院医学伦理委员会批准并遵循赫尔辛基宣言,收集先证者及其他家系成员病史资料,进行眼科专科检查并总结其临床特征;按照家系成员信息绘制系谱图并分析其遗传方式。该POAG家系在世患者纳入实验A组,家系其他成员为实验B组,C组为正常对照组20人,通过外周血或发囊提取出基因组DNA,应用梯度降温PCR扩增WDR36基因1-23外显子,然后对PCR产物直接测序检测基因突变,采用χ2检验对三组中突变频率作两两比较,bonferroni法进行校正,设定P0.0167时差异有统计学意义。 结果:该家系中有4代22人,确诊患者8例,其中男4例,女4例(2例去世)。6例在世患者确诊年龄为13—35岁。确诊时视野损害大多为早中期改变,最高眼压25.81—38.80 mmHg。随诊发现视野检查多无变化或仅为暗点深度增加,未见明显暗点范围扩大,眼压基本保持在正常范围内。该家系遗传学特点包括:①POAG在该家族中垂直传递,4代中每代均有患者;②患者双亲必有一人患病;③双亲无发病者则子女未见发病;④男女发病机率均等。共发现6个突变包括2个新突变(Pro381Pro、Gly549Arg)及4个已报道过的突变(Tyr216Pro、Ile264Val、Ala449Thr、Val727Val),其中Pro381Pro、Val727Val、Tyr216Pro、Ile264Val在三组间突变频率差异无统计学意义(P0.0167)。Ala449Thr只在A组Ⅱ3和Ⅲ6中检测出,与C组相比突变频率差异有统计学意义(P0.0167)。Gly549Arg在A组Ⅲ3、Ⅲ4和B组Ⅳ2、Ⅳ6、Ⅳ8中发现,未在C组检出,A组与C组相比突变频率差异有统计学意义(P0.0167),但B组与C组相比突变频率差异无统计学意义(P0.0167)。 结论:该家系遗传方式符合常染色体显性遗传。WDR36基因是该家族性POAG的相关致病基因,但单独WDR36基因突变不足以引起POAG发病,WDR36可能为其他致病基因的修饰基因。
[Abstract]:Objective: to study the clinical and genetic characteristics of a family with primary open-angle glaucoma from Jiangxi province and to investigate the possible role of WDR36 gene in the pathogenesis of POAG. Methods: the medical ethics committee of our hospital approved and followed the Helsinki Declaration, collected the medical history of proband and other family members, carried on the ophthalmology specialized examination and summarized its clinical characteristics. According to the information of the family members, the pedigree map was drawn and the genetic pattern was analyzed. The living patients of the POAG family were included in the experiment group A, and the other members of the family were 20 normal controls, the other members of the family were group B and group C, respectively. Genomic DNA was extracted from peripheral blood or hair sac. The exon 1-23 of WDR36 gene was amplified by gradient cooled PCR. The mutation was detected by direct sequencing of PCR products. The mutation frequency of the three groups was corrected by 蠂 2 test. The difference was statistically significant when P0.0167 was set. Results: there were 22 patients of 4 generations in this pedigree, 8 patients were diagnosed, including 4 males and 2 females. The age of diagnosis was 13 to 35 years old. Most of the visual field changes were early and metaphase changes at the time of diagnosis. The maximum intraocular pressure was 25.81-38.80 mm Hg.Most of the visual field did not change or only the depth of dark spot increased, but the range of dark spot was not obviously enlarged. The genetic characteristics of the pedigree include the vertical transmission of 1 Poag in the family in 4 generations with patients in each generation. One parent must have one patient with no disease in 3 parents and no disease in the children of 4 men and women. Six mutations including two new mutations (Pro381ProGly549 Arg) and four reported mutations, Tyr216Promonia Ile264ValA Ala449Thrfus Vala 727ValA, were found to have no significant difference in mutation frequency among the three groups (P 0.0167N. Ala449Thr), and there was no significant difference in the frequency of the mutations between the three groups (P 0.0167N. Ala449Thr). There was significant difference in mutation frequency between group C and group C (P 0.0167). Gly549 Arg was found in group A (鈪，

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