新疆维吾尔族和汉族非综合征性聋耳聋基因常见突变的研究

发布时间：2018-05-08 12:30

本文选题：GJB2基因 + SLC26A4基因　；参考：《新疆医科大学》2011年博士论文

【摘要】：目的：50%儿童期耳聋被认为与遗传因素有关,至今,与非综合征性耳聋相关的基因共有62个已被确认,在被发现的众多耳聋基因中,每个基因散在的突变位点数目众多,并且同一种表型可能由不同的基因导致,因而耳聋基因的基因和位点遗传异质性较高。由于在不同的地区和种族中耳聋基因突变谱和优势突变不同,新疆地处中西亚文化交汇处的中国西北边陲,是一个以维吾尔族为主体的多民族的地区,在千百年的民族迁徙和融合中,新疆地区维吾尔族耳聋基因突变谱和优势突变可能有其特点。本研究对新疆维吾尔族和汉族非综合征性耳聋人群常见耳聋基因突变位点进行检测,以揭示维吾尔族耳聋人群常见耳聋基因突变的特点及与汉族的区别。方法：选取新疆地区具有代表性的维吾尔族和汉族耳聋人群集中学校、医院和社会救助机构作为筛查对象,包括喀什市特教学校、喀什市残疾人联合会、喀什市语训学校、昌吉市特教学校、新疆维吾尔自治区残疾人联合会、乌鲁木齐语训学校和新疆医科大学第一附属医院耳鼻喉科门诊耳聋的患者作为非综合征性耳聋筛查对象。采集耳聋研究对象的基本资料,行听力学检查和全身体查,筛选出符合非综合征性聋的患者,同时选取新疆地区听力正常人群维吾尔族103人和汉族70人作为对照。抽取研究对象前臂静脉血样3-5ml,提取全血DNA,利用北京博奥生物有限公司设计开发的晶芯?九项遗传性耳聋基因检测芯片对所选样本进行耳聋基因突变检测,该芯片能检测GJB2、SLC26A4、mtDNA 12s rRNA和GJB3四个基因的九个位点35delG、176del16、235delC、299～300delAT、538CT、1555AG、1494CT、2168AG和IVS7-2AG的突变。对于检测过程中发现的突变位点探针信号缺失的样本。在美国ABI 3730测序仪进一步进行基因测序研究,以明确可能存在的新的突变。结果：在441例耳聋患者中筛选出无血缘关系的汉族和维吾尔族非综合征型聋患者共350例,其中维吾尔族199例,汉族151例。听力表现为双侧中重度以上感音神经性耳聋。筛选出的350人中,33人有明确家族史,即同胞兄弟姐妹、父母中还存在一个或一个以上耳聋患者。其中维吾尔族耳聋患者中有22人,汉族耳聋患者中有11人。对研究对象和对照组共523人进行突变基因检测,发现四例样本突变位点探针信号缺失,对四例样本进行基因测序。维吾尔族和汉族研究组常见耳聋基因的突变检出率分别为13.06%和32.45%,差异有统计学意义；GJB2基因在维吾尔族和汉族耳聋患者突变检出率分别为9.05%、16.56%,差异无统计学意义,235delC为两个民族耳聋患者的热点突变,35delG为维吾尔族耳聋患者的热点突变,187delG在维吾尔族耳聋患者中首次发现,也是新发现的GJB2基因的病理性突变；SLC26A4在维吾尔族和汉族耳聋患者中的突变检出率分别为2.01%、14.57%,差别有统计学意义,维吾尔族耳聋患者中的突变检出率明显低于汉族；mtDNA 12srRNA基因在维吾尔族和汉族耳聋患者中的突变检出率分别为2.01%、2.65%,差异无统计学意义；GJB3基因在两个民族耳聋患者中的突变检出率低。维吾尔族研究组有明确耳聋家族史的22人中,检测出突变3例,耳聋家族史人群检出的阳性率为13.64%(3/22)；汉族研究组有明确耳聋家族史11人中,检测出突变6例,耳聋家族史人群检出的阳性率为54.55%(6/11),两个民族中有耳聋家族史患者常见耳聋基因的阳性检出率经矫正卡方检验比较,差别有统计学意义,汉族研究组高于维吾尔族研究组。结论：本研究筛查对象为维吾尔族和汉族非综合征性聋耳聋人群,来源于喀什市特教学校、喀什市残疾人联合会、喀什市语训学校、昌吉市特教学校、新疆维吾尔自治区残疾人联合会、乌鲁木齐语训学校和新疆医科大学第一附属医院耳鼻喉科门诊就诊的患者,研究对象中既包括以维吾尔族聚居为主体的喀什、和田地区的患者,也包括了乌鲁木齐及周边地区汉族人口主要聚居地的患者,所以研究对象来源于两个民族的主体成分。维吾尔族研究组和对照组、汉族研究组和对照组常见耳聋基因突变检出率分别为13.06%、1.94%、32.45%和4.28%,维吾尔族研究组和汉族研究组常见耳聋基因突变检出率与各自对照组比较差别有统计学意义,研究组明显高于对照组,表明对耳聋人群进行常见耳聋基因检测对耳聋病因的诊断有积极的意义。维吾尔族研究组突变检出率明显低于汉族研究组,差别有统计学意义,表明维吾尔族研究组常见耳聋基因突变谱与汉族研究组不完全一样。GJB2基因在两个民族非综合征性耳聋人群中仍是耳聋相关基因的主要基因,但热点突变不尽相同。SLC26A4基因在维吾尔族研究组中的突变检出率明显低于汉族研究组,推测维吾尔族耳聋人群SLC26A4基因热点突变可能与蒙古人种不同,是否存在与高加索人种热点突变一致的位点还需要做进一步的研究来证实。所以说两个民族耳聋患者的耳聋基因突变谱并不完全相同。因此有必要对维吾尔族耳聋患者做进一步的基因序列分析和家系研究,来丰富维吾尔族耳聋基因的突变谱并确定优势突变。对耳聋基因常见突变检测不是研究的目的,通过耳聋基因诊断的结果,对耳聋患者及家属提供耳聋遗传咨询,就有关耳聋遗传的病因、遗传方式、诊断、防治和预后等相关问题进行沟通,对患者或其亲属生育子女时再患耳聋的风险进行评估,并提出建议和指导,然后结合客观、准确的生育指导和干预措施,将有助于从根本上预防和阻断遗传耳聋患儿的出生,从而达到提高我国人口的整体素质的目的。所以耳聋遗传咨询在耳聋的整体防治中具有重要的意义。
[Abstract]:Objective: 50% childhood deafness is considered to be associated with genetic factors. Up to now, 62 genes associated with non syndromic deafness have been identified. Among the numerous deafness genes found, the number of mutations per gene is numerous, and the same phenotype may be caused by different genes, thus the genes and loci of the deafness genes are found. The genetic heterogeneity is high. Due to the different mutation spectrum and dominant mutation of the deafness gene in different regions and races, Xinjiang is located in the northwest border of China and Western Asia. It is a multi-ethnic area with Uygur nationality as the main body. The mutation spectrum of the deafness gene of the Uygur in the Xinjiang area in thousands of years of ethnic migration and fusion. The characteristics of the mutation of the common deafness gene in the Uygur and Han non syndromic deafness people in Xinjiang were detected in this study to reveal the characteristics of the common deafness gene mutation in the Uygur deaf people and the difference from the Han people.
Methods: to select the representative Uygur and Han deaf people in Xinjiang to concentrate schools, hospitals and social assistance institutions as screening targets, including Kashi special education schools, Kashi disabled persons' Federation, Kashi language training school, Changji special education school, the Xinjiang Uygur Autonomous Region disabled people's Federation, Urumqi language training. In the Department of ENT, the First Affiliated Hospital of the First Affiliated Hospital of Xinjiang Medical University, the patients with deafness were screened as non syndromic deafness screening subjects. The basic data of the research subjects of deafness were collected, audiology and body examination were used to screen out patients with non syndromic deafness. At the same time, 103 Uygur people were selected from the normal hearing population in Xinjiang. 70 Han people as the control.
To extract 3-5ml from the forearm vein blood samples and extract DNA from the whole blood, nine genetic deafness gene detection chips were designed and developed by Beijing boo biological Co., Ltd. to detect the deafness gene mutation of the selected samples. The chip can detect the nine loci of GJB2, SLC26A4, mtDNA 12S rRNA and GJB3, 176del16235, 35delG, 176del16235. Mutations in delC, 299 to 300delAT, 538CT, 1555AG, 1494CT, 2168AG and IVS7-2AG. A sample of the deletion of the probe signal of the mutation site detected during detection. Further gene sequencing was carried out in the US ABI 3730 sequencer to identify possible new mutations.
Results: among the 441 Cases of deafness, 350 cases of Han and Uygur non syndromic deafness were screened out, of which 199 were Uygur and 151 in Han nationality. Hearing performance was bilateral moderate to severe sensorineural deafness. Among the 350 people, 33 had a clear family history, siblings and siblings, and parents still existed. One or more deafness patients, of whom 22 were Uygur deafness patients and 11 were Han deafness patients.
A total of 523 people in the study group and the control group were detected by mutation gene detection, and four sample mutation sites were found to be missing and four samples were sequenced. The mutation detection rates of the common deafness genes in the Uygur and Han study groups were 13.06% and 32.45%, respectively. The GJB2 gene was in Uygur and Han ears. The mutation detection rate of the deafness patients was 9.05%, 16.56%, the difference was not statistically significant. 235delC was the hot spot mutation of the deaf patients in two ethnic groups. 35delG was the hot mutation of the Uygur deafness. The 187delG was found in the Uygur deafness for the first time, and the pathological mutation of the newly discovered GJB2 gene; SLC26A4 in Uygur and Han people. The mutation detection rate in the deafness patients was 2.01% and 14.57% respectively. The mutation detection rate in the Uygur deafness was significantly lower than that of the Han nationality; the mutation detection rate of mtDNA 12srRNA gene in the Uygur and Han deafness patients was 2.01% and 2.65%, respectively, and the GJB3 gene was in two ethnic groups. The mutation detection rate in the deafness patients was low. In the Uygur study group, 3 of the 22 people with a clear family history of deafness were detected. The positive rate of the deaf family history was 13.64% (3/22); 6 cases were detected in the Han study group with a clear family history of deafness, and the positive rate was 54.55% (6/11), two in the family history of hearing loss (6/11), two The positive rate of the common deafness gene in the people with the history of deafness was compared with the corrected chi square test, the difference was statistically significant, and the Han study group was higher than the Uygur research group.
Conclusion: the objective of this study was the non syndromic deafness deafness people of Uygur and Han people, from Kashi special education school, Kashi disabled people's Federation, Kashi language training school, Changji special education school, the Xinjiang Uygur Autonomous Region Disabled Association, Urumqi language training school and the First Affiliated Hospital of Xinjiang Medical University. The patients in the outpatient department of the nasolaryngology included both the Kashi, the Uygur population and the patients in the Hotan area, and the patients in the main habitation of the Han population in Urumqi and the surrounding areas, so the subjects were derived from the main components of the two ethnic groups.
The common deafness gene mutations in the Uygur research group and the control group were 13.06%, 1.94%, 32.45% and 4.28%, respectively. The common deafness gene mutation rate in the Uygur research group and the Han study group was statistically significant compared with the control group, and the study group was obviously higher than the control group, indicating deafness in the study group. The common deafness gene detection in the population has positive significance for the diagnosis of the cause of deafness. The mutation detection rate of the Uygur study group is obviously lower than that of the Han study group, and the difference is statistically significant. It shows that the common deafness gene mutation spectrum of the Uygur study group is not exactly the same as the Han study group, and the.GJB2 gene is in the two ethnic non syndromic ears. The deaf population is still the main gene of deafness related genes, but the mutation detection rate of the.SLC26A4 gene in the Uygur study group is obviously lower than that of the Han study group. It is speculated that the SLC26A4 gene mutation of the Uygur deaf people may be different from the Mongolian species, and is the same as the hot spot mutation in the Caucasus. It is necessary to make further genetic sequence analysis and family studies in Uygur deafness to enrich the mutation spectrum of the Uygur deafness gene and determine the dominant mutation, so the mutation spectrum of the deafness of the two ethnic deafness patients is not exactly the same.
The detection of the common mutation of the deafness gene is not the purpose of the study. Through the results of the deafness gene diagnosis, the deafness patients and their families are provided with the genetic counseling on the deafness, the related problems related to the hereditary cause, the heredity, the diagnosis, the prevention and the prognosis of the deafness are communicated, and the risk of the deafness of the patients and their relatives when they have children is evaluated. It is important to estimate, put forward suggestions and guidance, and then combine objective and accurate reproductive guidance and intervention measures, which will help to prevent and block the birth of the children with hereditary deafness, so as to improve the overall quality of the population in our country. Therefore, the genetic counseling of deafness is of great significance in the overall prevention and treatment of deafness.

【学位授予单位】：新疆医科大学
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R764.43

【引证文献】