本文關鍵詞： 家族性原發(fā)性開角型青光眼 遺傳方式 WDR36基因 基因突變　出處：《南昌大學》2010年碩士論文　論文類型：學位論文

【摘要】： 目的:研究一個江西籍原發(fā)性開角型青光眼家系的臨床及遺傳學特點;檢測該家系成員是否存在WDR36基因突變,探討WDR36基因在該POAG家系發(fā)病中可能的作用。 方法:經我院醫(yī)學倫理委員會批準并遵循赫爾辛基宣言,收集先證者及其他家系成員病史資料,進行眼科�？茩z查并總結其臨床特征;按照家系成員信息繪制系譜圖并分析其遺傳方式。該POAG家系在世患者納入實驗A組,家系其他成員為實驗B組,C組為正常對照組20人,通過外周血或發(fā)囊提取出基因組DNA,應用梯度降溫PCR擴增WDR36基因1-23外顯子,然后對PCR產物直接測序檢測基因突變,采用χ2檢驗對三組中突變頻率作兩兩比較,bonferroni法進行校正,設定P0.0167時差異有統(tǒng)計學意義。 結果:該家系中有4代22人,確診患者8例,其中男4例,女4例(2例去世)。6例在世患者確診年齡為13—35歲。確診時視野損害大多為早中期改變,最高眼壓25.81—38.80 mmHg。隨診發(fā)現(xiàn)視野檢查多無變化或僅為暗點深度增加,未見明顯暗點范圍擴大,眼壓基本保持在正常范圍內。該家系遺傳學特點包括:①POAG在該家族中垂直傳遞,4代中每代均有患者;②患者雙親必有一人患病;③雙親無發(fā)病者則子女未見發(fā)病;④男女發(fā)病機率均等。共發(fā)現(xiàn)6個突變包括2個新突變(Pro381Pro、Gly549Arg)及4個已報道過的突變(Tyr216Pro、Ile264Val、Ala449Thr、Val727Val),其中Pro381Pro、Val727Val、Tyr216Pro、Ile264Val在三組間突變頻率差異無統(tǒng)計學意義(P0.0167)。Ala449Thr只在A組Ⅱ3和Ⅲ6中檢測出,與C組相比突變頻率差異有統(tǒng)計學意義(P0.0167)。Gly549Arg在A組Ⅲ3、Ⅲ4和B組Ⅳ2、Ⅳ6、Ⅳ8中發(fā)現(xiàn),未在C組檢出,A組與C組相比突變頻率差異有統(tǒng)計學意義(P0.0167),但B組與C組相比突變頻率差異無統(tǒng)計學意義(P0.0167)。 結論:該家系遺傳方式符合常染色體顯性遺傳。WDR36基因是該家族性POAG的相關致病基因,但單獨WDR36基因突變不足以引起POAG發(fā)病,WDR36可能為其他致病基因的修飾基因。
[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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