【摘要】：耳聾,即聽力障礙,是指人們對聲音的大小及辨識度下降的表現(xiàn)。聽力障礙在各種身體殘疾中所占比例較高,嚴(yán)重影響患者的日常生活。在遺傳性非綜合征耳聾患者中,約有21%是由GJB2基因突變引起的,而其中最常見的是235位點一個胞嘧啶缺失(235delC)所致框移突變造成的。本實驗針對山東省內(nèi),主要是東營、聊城、濟(jì)南地區(qū)收集病例,進(jìn)行GJB2 235delC突變的流行病學(xué)調(diào)查。 第一部分山東省內(nèi)部分地區(qū)遺傳性非綜合征型耳聾患者臨床資料的收集與GJB2 235delC突變的篩查 目的：探討山東省內(nèi)先天性非綜合征型聾(NSHI)患者的GJB2 235delC突變頻率和聽力學(xué)表型特點,并進(jìn)行幾個典型家系的遺傳分析。 方法：以完全自愿為原則,收集前來山東大學(xué)齊魯醫(yī)院耳鼻喉門診及病房的本省NSHI患者及濟(jì)南市、東營市、聊城市及其他地區(qū)聾兒康復(fù)機(jī)構(gòu)與特殊教育學(xué)校符合條件的非綜合征耳聾患者共252例作為實驗組,其直系家屬作為有明確家族史但聽力表型正常且無全身系統(tǒng)疾病的健康志愿者208例作為對照組,提取外周血DNA進(jìn)行GJB2基因聚合酶鏈反應(yīng)(PCR)擴(kuò)增,使用耳聾基因GJB2 235delC檢測試劑盒標(biāo)記PCR產(chǎn)物進(jìn)行熒光檢測,依據(jù)DNA擴(kuò)增的熒光曲線模式分析是否存在GJB2基因235delC位點純合或雜合突變,并對檢測結(jié)果進(jìn)行匯總,利用統(tǒng)計學(xué)方法進(jìn)行分析,同時選取幾個典型家系進(jìn)行遺傳分析。 結(jié)果：1.GJB2 235delC突變檢出率：在實驗組252例NSHI患者GJB2 235delC突變總檢出率21.04%,對照組208總檢出率17.31%。實驗組與對照組基因型構(gòu)成比之間做卡方檢驗,p=0.001,兩組間基因型構(gòu)成比差異具有統(tǒng)計學(xué)意義。 2. GJB2 235delC等位基因頻率：實驗組等位基因頻率17.06%(86/504),對照組等位基因頻率9.13%(38/416),兩組之間235delC等位基因頻率(17.06%和9.13%)做卡方檢驗,p=0.650(P0.050)無統(tǒng)計學(xué)意義。 3.標(biāo)本來源地區(qū)及地區(qū)間235delC檢出率差異的統(tǒng)計 本實驗中252例NSHI患者來自山東省內(nèi)各地,主要來自東營、聊城、濟(jì)南及其他各地區(qū),用多個樣本率的卡方檢驗進(jìn)行235delC檢出率分布差異的統(tǒng)計學(xué)分析：東營與聊城P=0.037 (P0.05);東營與濟(jì)南P=0.635 (P0.050);東營與省內(nèi)其他地市P=0.823 (P0.050);東營與山東省平均水平P=0.502 (P0.050);聊城與濟(jì)南P=0.030 (P0.05);聊城與其他地市P=0.053 (P0.050);聊城與山東省平均水平P=0.072 (P0.050);濟(jì)南與其他地市P=0.829 (P0.050);濟(jì)南與山東省P=0.313 (P0.050);其他地市與平均水平P=0.462 (P0.050)。即聊城市NSHI患者GJB2 235delC突變率明顯低于東營市及濟(jì)南市,而與其他地區(qū)無明顯差異,山東省除聊城市NSHI患者235delC突變率較低外,其余并無明顯地域差異。 結(jié)論：山東省內(nèi)遺傳性非綜合征型耳聾患者中GJB2基因235delC突變檢出率為21.04%,各地市除聊城市此基因突變檢出率較低(12.36%),明顯低于東營市及濟(jì)南市,山東省內(nèi)并無明顯地域差異,等位基因頻率為17.06%,具有明確家族史的健康志愿者中GJB2基因235delC突變檢出率為17.31%,等位基因頻率為9.13%。無論是在患者還是在有明確家族史的健康志愿者中,GJB2 235delC突變率均處于較高水平。 第二部分?jǐn)y帶GJB2基因235delC突變的4個耳聾家系的遺傳特點分析 目的：對山東省內(nèi)先天性非綜合征型聾(NSHI)患者的GJB2 235delC基因突變檢測結(jié)果匯總后,選取其中典型的4個家系進(jìn)行遺傳分析,探討此位點突變與NSHI的關(guān)系。 方法：本次實驗所入選患者家庭成員進(jìn)行全面的信息采集及體格檢查,并進(jìn)行純音測聽,同時檢測是否攜帶235delC突變,選取幾個典型家系畫家系圖進(jìn)行遺傳分析。 結(jié)果：此次實驗中所選GJB2 235delC家系臨床資料匯總?cè)缦卤硭荆?結(jié)論：GJB2基因為常染色隱性遺傳,單純的235 delC雜合突變并不會導(dǎo)致耳聾,但本次實驗中僅進(jìn)行這一個位點的檢測,因此并不能單純以此結(jié)果來判定。當(dāng)復(fù)合病理性突變存在時,則可導(dǎo)致重度或極重度的感音神經(jīng)性聾。
[Abstract]:Deafness, or hearing impairment, refers to a decline in the size and recognition of sound. Hearing impairment accounts for a high proportion of all physical disabilities and seriously affects the daily lives of patients. About 21% of hereditary nonsyndromic deafness patients are caused by mutations in the GJB2 gene, the most common of which is a cytosine at 235 sites. This study was conducted to investigate the epidemiology of GJB2 235 delC mutation in Dongying, Liaocheng and Jinan areas of Shandong Province.
Part I Collection of clinical data and screening of GJB2 235delC mutation in hereditary non-syndromic deafness patients in some areas of Shandong Province
Objective: To investigate the frequency of GJB2 235delC mutation and audiological phenotype in patients with congenital non-syndromic hearing loss (NSHI) in Shandong Province, and to analyze the genetic characteristics of several typical families.
Methods: A total of 252 NSHI patients from Shandong University Qilu Hospital, Jinan City, Dongying City, Liaocheng City and other areas who met the requirements of special education schools and non-syndromic deafness rehabilitation institutions were selected as the experimental group. Their immediate family members were defined as families. 208 healthy volunteers with normal hearing phenotype and no systemic diseases served as control group. Peripheral blood DNA was extracted for amplification of GJB2 gene by polymerase chain reaction (PCR). The PCR products were labeled with deaf gene GJB2 235 delC detection kit for fluorescence detection. The existence of GJB2 gene 235 D was analyzed according to the fluorescence curve pattern of DNA amplification. Homozygous or heterozygous mutations at the elC locus were analyzed by statistical method and the results were summarized.
The detection rate of GJB2 235 delC mutation was 21.04% in the experimental group and 17.31% in the control group. Chi-square test was performed between the experimental group and the control group, p=0.001, and the difference was statistically significant.
2. GJB2 235 delC allele frequency: The allele frequency was 17.06% (86/504) in the experimental group and 9.13% (38/416) in the control group. The frequency of 235 delC allele between the two groups (17.06% and 9.13%) was chi-square test, P = 0.650 (P 0.050).
3. statistics on the difference of 235delC detection rates between regions and regions of specimen origin
In this study, 252 NSHI patients from all over Shandong Province, mainly from Dongying, Liaocheng, Jinan and other regions, using multiple sample rate chi-square test for 235 delC detection rate distribution differences of statistical analysis: Dongying and Liaocheng P = 0.037 (P 0.05); Dongying and Jinan P = 0.635 (P 0.050); Dongying and other cities in the province P = 0.823 (P 0.050); Dongying and Shandong average P = 0.502 (P 0.050); Liaocheng and Jinan P = 0.030 (P 0.05); Liaocheng and other cities P = 0.053 (P 0.050); Liaocheng and Shandong average P = 0.072 (P 0.050); Jinan and other cities P = 0.829 (P 0.050); Jinan and Shandong P = 0.313 (P 0.050); other cities and average P = 0.462 (P 0.050). The mutation rate of GJB2 235delC was significantly lower in Liaocheng than in Dongying and Jinan, but there was no significant difference with other areas.
Conclusion: The detection rate of GJB2 gene 235delC mutation was 21.04% in inherited non-syndromic deafness patients in Shandong Province. The detection rate of GJB2 gene 235delC mutation was lower in all cities except Liaocheng City (12.36%) than that in Dongying City and Jinan City. There was no significant regional difference in Shandong Province. The allele frequency was 17.06%. There was a clear family history of healthy volunteers. The mutation rate of 235delC in GJB2 gene was 17.31% and the allele frequency was 9.13%. The mutation rate of GJB2 235delC was high in both patients and healthy volunteers with a clear family history.
The second part is the genetic analysis of 4 deaf families carrying GJB2 gene 235delC mutation.
Objective: To investigate the relationship between GJB2 235delC gene mutation and NSHI in 4 families of non-syndromic hearing loss (NSHI) patients in Shandong Province.
Methods: Family members of the selected patients were given comprehensive information collection and physical examination, and pure tone audiometry was carried out. At the same time, 235 delC mutation was detected. Several typical family painters were selected for genetic analysis.
Results: the clinical data of the selected families of GJB2 235delC were summarized in the following table:
CONCLUSION: GJB2 gene is an autochromatic recessive inheritance. A simple 235 delC heterozygous mutation does not result in deafness, but only this site is detected in this experiment, so it can not be judged simply by this result.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R764

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本文編號：2250744