山东省部分地区252例先天性非综合征型耳聋患儿GJB2 235delC突变分析
发布时间：2018-09-19 16:56
【摘要】：耳聋,即听力障碍,是指人们对声音的大小及辨识度下降的表现。听力障碍在各种身体残疾中所占比例较高,严重影响患者的日常生活。在遗传性非综合征耳聋患者中,约有21%是由GJB2基因突变引起的,而其中最常见的是235位点一个胞嘧啶缺失(235delC)所致框移突变造成的。本实验针对山东省内,主要是东营、聊城、济南地区收集病例,进行GJB2 235delC突变的流行病学调查。 第一部分山东省内部分地区遗传性非综合征型耳聋患者临床资料的收集与GJB2 235delC突变的筛查 目的：探讨山东省内先天性非综合征型聋(NSHI)患者的GJB2 235delC突变频率和听力学表型特点,并进行几个典型家系的遗传分析。 方法：以完全自愿为原则,收集前来山东大学齐鲁医院耳鼻喉门诊及病房的本省NSHI患者及济南市、东营市、聊城市及其他地区聋儿康复机构与特殊教育学校符合条件的非综合征耳聋患者共252例作为实验组,其直系家属作为有明确家族史但听力表型正常且无全身系统疾病的健康志愿者208例作为对照组,提取外周血DNA进行GJB2基因聚合酶链反应(PCR)扩增,使用耳聋基因GJB2 235delC检测试剂盒标记PCR产物进行荧光检测,依据DNA扩增的荧光曲线模式分析是否存在GJB2基因235delC位点纯合或杂合突变,并对检测结果进行汇总,利用统计学方法进行分析,同时选取几个典型家系进行遗传分析。 结果：1.GJB2 235delC突变检出率：在实验组252例NSHI患者GJB2 235delC突变总检出率21.04%,对照组208总检出率17.31%。实验组与对照组基因型构成比之间做卡方检验,p=0.001,两组间基因型构成比差异具有统计学意义。 2. GJB2 235delC等位基因频率：实验组等位基因频率17.06%(86/504),对照组等位基因频率9.13%(38/416),两组之间235delC等位基因频率(17.06%和9.13%)做卡方检验,p=0.650(P0.050)无统计学意义。 3.标本来源地区及地区间235delC检出率差异的统计 本实验中252例NSHI患者来自山东省内各地,主要来自东营、聊城、济南及其他各地区,用多个样本率的卡方检验进行235delC检出率分布差异的统计学分析：东营与聊城P=0.037 (P0.05);东营与济南P=0.635 (P0.050);东营与省内其他地市P=0.823 (P0.050);东营与山东省平均水平P=0.502 (P0.050);聊城与济南P=0.030 (P0.05);聊城与其他地市P=0.053 (P0.050);聊城与山东省平均水平P=0.072 (P0.050);济南与其他地市P=0.829 (P0.050);济南与山东省P=0.313 (P0.050);其他地市与平均水平P=0.462 (P0.050)。即聊城市NSHI患者GJB2 235delC突变率明显低于东营市及济南市,而与其他地区无明显差异,山东省除聊城市NSHI患者235delC突变率较低外,其余并无明显地域差异。 结论：山东省内遗传性非综合征型耳聋患者中GJB2基因235delC突变检出率为21.04%,各地市除聊城市此基因突变检出率较低(12.36%),明显低于东营市及济南市,山东省内并无明显地域差异,等位基因频率为17.06%,具有明确家族史的健康志愿者中GJB2基因235delC突变检出率为17.31%,等位基因频率为9.13%。无论是在患者还是在有明确家族史的健康志愿者中,GJB2 235delC突变率均处于较高水平。 第二部分携带GJB2基因235delC突变的4个耳聋家系的遗传特点分析 目的：对山东省内先天性非综合征型聋(NSHI)患者的GJB2 235delC基因突变检测结果汇总后,选取其中典型的4个家系进行遗传分析,探讨此位点突变与NSHI的关系。 方法：本次实验所入选患者家庭成员进行全面的信息采集及体格检查,并进行纯音测听,同时检测是否携带235delC突变,选取几个典型家系画家系图进行遗传分析。 结果：此次实验中所选GJB2 235delC家系临床资料汇总如下表所示： 结论：GJB2基因为常染色隐性遗传,单纯的235 delC杂合突变并不会导致耳聋,但本次实验中仅进行这一个位点的检测,因此并不能单纯以此结果来判定。当复合病理性突变存在时,则可导致重度或极重度的感音神经性聋。
[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.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R764
[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.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R764
【参考文献】
相关期刊论文 前3条
1 于飞;戴朴;韩东一;曹菊阳;康东洋;刘新;张昕;李梅;刘丽贤;袁慧军;杨伟炎;吴柏林;;中国部分地区非综合征型耳聋患者GJB2基因233～235delC突变频率分析[J];中国耳鼻咽喉头颈外科;2006年04期
2 关静;郭玉芬;徐百成;赵亚丽;李庆忠;王秋菊;;中国西北地区部分语前聋患者GJB2基因突变的分子流行病学研究[J];解放军医学杂志;2006年04期
3 于飞;韩东一;戴朴;康东洋;张昕;刘新;朱庆文;袁永一;孙R，
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