摘要
耳聋是导致言语交流障碍的人类重大疾病,在每1000名新生儿中就有1名先天性耳聋患者。遗传性耳聋具有高度的遗传异质性,而且,在不同的地区和不同的人群中耳聋基因的突变频率、突变方式和热点突变有很大的差异。目前研究显示,在众多已明确的耳聋基因中,在人群中有较高突变频率的耳聋基因有GJB2基因、SLC26A4基因、线粒体DNA12SrRNA基因、TMC1基因和POU3F4基因等。近几年,针对这几个常见耳聋基因在我国人群中的流行分布情况的研究已经有所进展和发现,国内的这些研究大部分是在汉族人群中进行的,在少数民族耳聋人群中常见耳聋基因的分子流行病学研究相对较少。因此,本研究对我国西北少数民族群众较集中的地区开展耳聋基因的分子流行病学研究,以了解耳聋基因在中国北方少数民族地区和少数民族人群的流行分布情况,我们研究的主要内容由以下两部分组成:
第一部分中国西北少数民族和汉族耳聋患者GJB2基因突变分子流行病学研究
本研究在我国西北地区维吾尔族、回族、蒙古族及汉族共559例耳聋患者中进行GJB2基因突变检测,在四个民族中均检测到GJB2基因突变,GJB2基因突变在各民族耳聋患者中有较高的携带率。四个民族中均检测出235delC突变,而且,235delC突变是每个民族最常见的突变方式,其中,235delC突变携带率汉族最高(15.2%),蒙古族最低(3.8%)。四个民族均检测到299-300delAT。在维吾尔族患者中235delC和35delG均有较高的突变携带率(7.1%和5.2%),并在维吾尔族患者中检测到两种新的突变类型(187delG和311del14)。在回族患者中检测到2例35delG突变患者。回族、蒙古族和汉族的GJB2基因分子流行病学特征基本一致。
第二部分新疆维吾尔自治区不同民族聋哑学生SLC26A4基因和线粒体DNA12SrRNAA1555G突变分子流行病学研究
本研究在新疆维吾尔自治区汉族、维吾尔族、哈萨克族、柯尔克孜族、回族和蒙古族402例感音神经性耳聋患者中进行线粒体DNA12SrRNA A1555G和SLC26A4基因突变检测,在汉族和维吾尔族患者中检测出线粒体DNA12SrRNAA1555G突变,突变携带率分别为3.8%和1.4%,线粒体DNA12SrRNA A1555G突变是该地区汉族和维吾尔族人群常见的耳聋致病基因。在汉族和维吾尔族患者中检测出SLC26A4基因IVS7-2A＞G突变,突变携带率分别为9.5%和0.9%,IVS7-2A＞G突变是汉族耳聋患者重要的致病突变,汉族和维吾尔族人群SLC26A4基因热点突变存在差异。需要对维吾尔族患者SLC26A4基因进行更全面的检测,以及扩大该地区其他民族的耳聋人群的样本量,以进一步明确该地区不同民族聋病基因的分子流行病学特征。
Deafness is one of significant diseases of mankind,which is the cause of speech impediments communictation.Approximately one in 1000 children is affected by severe or profound hearing loss at birth or during early childhood.Genetic deafness is highly genetic heterogeneity,and the rate of mutation frequency of the deafness gene is great difference in different area and crowd.In deafness genes cloned,GJB2, SLC26A4,DNA12SrRNA,TMC1 and POU3F4 have the high mutation frequency in population from different ethnic origns.In recent years,the research about the prevevlance of these common deafness genes in Chinese population had the progress and the discovery,but these studies were mainly made in the Chinese Han population,and molecular epidemiology research about the deafness gene in Chinese Minority Groups are relatively few.So we study the prevelance of these common deafness genes mutations in the patients in northwest China where many Minority Groups are living in.This thesis comprised two parts and the details were described as following.
The first part:Molecular epidemiological study of GJB2 mutations in deafness patients from Minority Groups and Han ethnic origin in northwest China.
This sdudy was to investigate the prevalance and characteristics of GJB2 mutations in 559 sporadic patients with sensorineural hearing loss(SNHL) from Uigur,Hui,Mongolian and Han nationality in northwest China.GJB2 mutations were detected in four nationalities,and there was a rather high mutation rate of GJB2 in Uigur,Hui,Mongolian and Han SNHL patients.235delC and 299-300delAT were detected in the patients of the four groups,235de1C was the most common mutation in every groups.The highest carrier frequency of 235delC is 15.2%in Han deaf-mute students,and the lowest is 3.8%in Mongolian patients.235delC and 35delG mutations were found in Uigur deaf-mute students,and the carrier frequency of 235delC and 35delG mutations is 7.1%and 5.2%respectivley.Two novel mutions were found in Uigur patients.Two patients with 35delG mutation were found in Hui deaf-mute students.The characteristics of GJB2 mutations of Hui and Mongolian patients were basically consistent with one of Han group.
The second part:Molecular epidemiological study of SLC26A4 and mtDNA12SrRNAA1555G mutations in deaf-mute students from different ethnic orign in Xinjiang Uigur Automonous Region of China
This study was to determine the prevalance and characteristics of SLC26A4 and mitochondrial DNA(mtDNA) A1555G mutations in 402 patients with sensorineural hearing loss(SNHL) from Xinjiang Uigur Automonous Region,China. The homoplasmic mtDNA A1555G mutation was found in Han and Uigur deaf-mute students,and the carrier frequency of A1555G was 3.8%and 1.4%,respectively. The IVS7-2A＞G mutation of SLC26A4 were detected in Han and Uigur patients,the carrier frequency of IVS7-2A＞G was 9.5%and 0.9%,respectively.IVS7-2A＞G was the common mutation of SLC26A4 in Han patients,and the hot mutation of SLC26A4 was different between Han and Uigur deaf-mute students.More comprehensive examination of SLC26A4 mutations were needed to undergo in Uigur patiens,and the muatations of deafness gene were detected in more samples from other nationalities in order to determine the characteristic of the molecular epidemiology of deafness genes in northwest China.
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