河北省滄州地區(qū)非綜合征性耳聾患者易感基因篩查分析
發(fā)布時間：2018-07-16 22:06
【摘要】：耳聾可導(dǎo)致與他人交流、溝通障礙,是最常見先天性疾患之一,本世紀初在全國范圍內(nèi)進行第二次大規(guī)模的殘疾人取樣調(diào)查分析結(jié)果表明目前聽障患者數(shù)量可達2780萬,當中約27%(127萬)存在語言殘疾,居總殘障人士首位。國內(nèi)出生缺陷性疾病之中先天性聽力障礙最為常見。根據(jù)統(tǒng)計每一年有3萬余兒童成為殘障人士隊伍中的新成員,這些兒童年齡均不超過7歲。還有遲發(fā)型或(和)藥物誘發(fā)性耳聾患者人數(shù)逐年增高。人類基因組計劃的完成使得基因相關(guān)領(lǐng)域的科學(xué)技術(shù)的發(fā)展,隨之而來的有關(guān)先天性遺傳相關(guān)性聾病患者的基因?qū)W研究同樣獲得重大突破,目前普遍認為耳聾患者的病因越來越偏向于遺傳因素,此部分患者占耳聾患者人數(shù)的66%。80%的聽力損失患者除耳聾外不伴隨其他癥狀,稱之為非綜合癥性耳聾(nonsyndromic hearing impairment.NSHI)。多個基因與遺傳性聽力障礙存在相關(guān),其中大部分遺傳性耳聾的相關(guān)基因定位于GJB2、SLC26A4和線粒體DNA病理突變。近年通過國內(nèi)大規(guī)模耳聾基因篩查工作的開展發(fā)現(xiàn)在國民聽力正常人群中存在較高的聾病相關(guān)易感基因突變的攜帶率,這部分患者將這種基因遺傳給下一代,大大增加他們生育聾兒的風(fēng)險。因此早診斷,早干預(yù),對減少本地區(qū)先天性耳聾患者的出生率,及預(yù)后、建議選擇配偶等方面具有非常重要的意義。目的:調(diào)查河北省滄州地區(qū)非綜合征性耳聾患者聾病易感基因突變分子機理。方法:河北省滄州特殊教育學(xué)校學(xué)生及滄州市聽力診療中心就診的散發(fā)病例中診斷為先天性非綜合征性耳聾的患者共358例,告訴患者及其家長本次調(diào)查研究目的,并填寫問卷調(diào)查表及簽署知情同意書;檢查每位患者行全身體格檢查除外有其他癥狀的綜合征性耳聾;給每位患者進行純音電聽閾值檢查(GSI-61純音測聽儀)及聲導(dǎo)抗(Madsen聲導(dǎo)抗檢測儀),3歲以下耳聾患者行腦干誘發(fā)電位。抽出每位患者外周靜脈血5ml,給予乙二胺四乙酸二鉀抗凝,放入4℃冰箱中進行保存。全血樣品完全解凍后,按照指示劑說明提取DNA。用紫外分光光度計測定樣品的濃度和純度。參照試劑盒說明書進行PCR擴增,雜交和洗滌后檢測GJB2、SLC26A4、線粒體DNA 12SrRNA、GJB3聾病相關(guān)的4個基因的9個突變位點:GJB2c.235delG、GJB2 c.235delC、GJB2 c.176del16、GJB2 c.299del AT、SLC26A4c.2168AG、SLC26A4 IVS7-2AG、線粒體DNAC1494T和線粒體DNA A1555G,GJB3 c.538CT。結(jié)果:358名受試者中有占總?cè)藬?shù)19.5%(70人)檢測出耳聾相關(guān)基因突變,其中GJB2基因突變患者為39人,占總?cè)藬?shù)的10.89%,GJB2235delc純合突變患者為18人,299delAT純合突變患者為3人,del235c位點突變單雜合突變患者為9人,復(fù)合雜合突變患者為9人;299delAT檢出率占25%,176del16檢出率占5.12%,235delC檢出率為74.33%;SLC26A4突變患者28人,占7.82%,IVS7-2AG純合突變患者為4人,IVS7-2AG單雜合突變患者為20人,復(fù)合雜合突變患者為4人。線粒體DNAA1555G均質(zhì)突變患者僅為1人,占總?cè)藬?shù)0.27%。GJB3突變患者為2人占總?cè)藬?shù)0.54%。將受試者根據(jù)就診方式不同分為特教組及散發(fā)組,特教組致病基因總檢出率為15.35%(37/241),散發(fā)組總檢出率為28.20%(33/117),P0.01,兩組間存在差異,GJB2,SLC26A4,線粒體DNA,GJB3基因突變在特教組檢出率分別為(10.3%,4.9%,0,0)。而散發(fā)組上述基因檢出率為(11.7%,13.6%,0.85%,1.75%),GJB2基因突變率在兩組間不存在差異P0.05,而SLC26A4基因突變率在兩者間存在差異,P0.01,具有統(tǒng)計學(xué)意義。結(jié)論:通過檢測聾病基因檢測位點,進行聾病分子診斷,對本地區(qū)預(yù)防耳聾發(fā)生、婚育、指導(dǎo)康復(fù)及評估預(yù)后提供依據(jù)。聾病相關(guān)基因突變檢出率普遍低于全國水平,或許存在環(huán)境或其他遺傳因素在本區(qū)域內(nèi)發(fā)揮作用。
[Abstract]:Deafness can lead to communication with others, communication barriers, and one of the most common congenital disorders. At the beginning of this century, second large-scale persons with disabilities sampling survey showed that the number of hearing impaired patients reached 27 million 800 thousand, of which about 27% (1 million 270 thousand) were handicapped and the first. Congenital hearing impairment is the most common in the disease. According to statistics, more than 3 million children have become a new member of the disabled people each year. These children are not more than 7 years old. And the number of delayed or (and) drug induced deafness is increasing year by year. The completion of the human genome project makes the science and technology in the field of gene related. Development, the genetic study of patients with congenital genetic related deafness is also a major breakthrough. It is widely believed that the cause of the deafness is becoming more and more hereditary, and this part of the 66%.80% hearing loss patients, which is deafness, is not accompanied by other symptoms, and is called non syndrome. Nonsyndromic hearing impairment.NSHI. Multiple genes are associated with hereditary hearing impairment, and most of the genetic deafness related genes are located in GJB2, SLC26A4 and mitochondrial DNA pathological mutations. In recent years, the development of large-scale hearing loss screening in China has been found to be higher in people with normal hearing. The incidence of mutations in the susceptible genes of the deafness, which is inherited to the next generation, greatly increases their risk of having deaf children. Therefore, early diagnosis and early intervention are of great significance to reduce the birth rate and prognosis of the local deafness, and recommend the choice of spouses. Objective: To investigate Hebei Methods: 358 cases of congenital non syndromic deafness were diagnosed in the Cangzhou special education school and the hearing diagnosis center in Cangzhou, Hebei Province, and 358 cases with congenital non syndromic deafness were diagnosed in the Cangzhou special education school in Hebei province. The volume of the questionnaire and the signing of the informed consent; the general physical examination of each patient except for the syndrom deafness with other symptoms; the pure tone threshold examination (GSI-61 pure tone audiometry) and the acoustic conductance (Madsen acoustic conductivity detector) for each patient and the brainstem evoked potential of the deafness under 3 years of age. Vein blood 5ml, give ethylene diamine tetra acetic acid two potassium anticoagulant, put it in 4 centigrade refrigerator and store it. After complete thawing of the whole blood sample, the concentration and purity of the samples are determined by the ultraviolet spectrophotometer according to the indicator. PCR amplification, GJB2, SLC26A4, mitochondrial DNA 12SrRNA, GJB3 deafness after the hybridization and cleaning of the reagent box are amplified. 9 mutations of the 4 genes related to the disease: GJB2c.235delG, GJB2 c.235delC, GJB2 c.176del16, GJB2 c.299del AT, SLC26A4c.2168AG, SLC26A4 IVS7-2AG, mitochondrial DNAC1494T and mitochondrial DNA, which accounted for 19.5% (70) of the total number of mutations in the deafness related genes. The patients were 39, accounting for 10.89% of the total number, 18 GJB2235delc homozygous mutations, 3 homozygous mutations, 9 heterozygous mutations in del235c site and 9 in complex heterozygous mutations, 25% in 299delAT, 5.12% in 176del16, 74.33% in 235delC, 28 in SLC26A4, 7.82% in SLC26A4. The IVS7-2AG homozygous mutation was 4, the IVS7-2AG single heterozygous mutation was 20, the complex heterozygous mutation was 4. The mitochondrial DNAA1555G homozygous mutation was only 1, and the total number of 0.27%.GJB3 mutations was 2 of the total number 0.54%.. The subjects were divided into special and sporadic groups according to the different ways of visiting. The detection rate was 15.35% (37/241), the total detection rate of the sporadic group was 28.20% (33/117), and there were differences among the two groups, GJB2, SLC26A4, and mitochondrial DNA, and the detection rates of GJB3 gene mutations in the special group were (10.3%, 4.9%, 0,0), and the detection rates of the genes were (11.7%, 13.6%, 0.85%, 1.75%), and the mutation rate of GJB2 gene was not different P0.05 in the two groups. The mutation rate of SLC26A4 gene is different between the two and P0.01, which has statistical significance. Conclusion: the detection of deafness gene detection site and molecular diagnosis of deafness can provide a basis for prevention of deafness, marriage and breeding, guidance for rehabilitation and evaluation of prognosis. Environmental or other genetic factors play a role in the region.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R764.43
本文編號：2127812
[Abstract]:Deafness can lead to communication with others, communication barriers, and one of the most common congenital disorders. At the beginning of this century, second large-scale persons with disabilities sampling survey showed that the number of hearing impaired patients reached 27 million 800 thousand, of which about 27% (1 million 270 thousand) were handicapped and the first. Congenital hearing impairment is the most common in the disease. According to statistics, more than 3 million children have become a new member of the disabled people each year. These children are not more than 7 years old. And the number of delayed or (and) drug induced deafness is increasing year by year. The completion of the human genome project makes the science and technology in the field of gene related. Development, the genetic study of patients with congenital genetic related deafness is also a major breakthrough. It is widely believed that the cause of the deafness is becoming more and more hereditary, and this part of the 66%.80% hearing loss patients, which is deafness, is not accompanied by other symptoms, and is called non syndrome. Nonsyndromic hearing impairment.NSHI. Multiple genes are associated with hereditary hearing impairment, and most of the genetic deafness related genes are located in GJB2, SLC26A4 and mitochondrial DNA pathological mutations. In recent years, the development of large-scale hearing loss screening in China has been found to be higher in people with normal hearing. The incidence of mutations in the susceptible genes of the deafness, which is inherited to the next generation, greatly increases their risk of having deaf children. Therefore, early diagnosis and early intervention are of great significance to reduce the birth rate and prognosis of the local deafness, and recommend the choice of spouses. Objective: To investigate Hebei Methods: 358 cases of congenital non syndromic deafness were diagnosed in the Cangzhou special education school and the hearing diagnosis center in Cangzhou, Hebei Province, and 358 cases with congenital non syndromic deafness were diagnosed in the Cangzhou special education school in Hebei province. The volume of the questionnaire and the signing of the informed consent; the general physical examination of each patient except for the syndrom deafness with other symptoms; the pure tone threshold examination (GSI-61 pure tone audiometry) and the acoustic conductance (Madsen acoustic conductivity detector) for each patient and the brainstem evoked potential of the deafness under 3 years of age. Vein blood 5ml, give ethylene diamine tetra acetic acid two potassium anticoagulant, put it in 4 centigrade refrigerator and store it. After complete thawing of the whole blood sample, the concentration and purity of the samples are determined by the ultraviolet spectrophotometer according to the indicator. PCR amplification, GJB2, SLC26A4, mitochondrial DNA 12SrRNA, GJB3 deafness after the hybridization and cleaning of the reagent box are amplified. 9 mutations of the 4 genes related to the disease: GJB2c.235delG, GJB2 c.235delC, GJB2 c.176del16, GJB2 c.299del AT, SLC26A4c.2168AG, SLC26A4 IVS7-2AG, mitochondrial DNAC1494T and mitochondrial DNA, which accounted for 19.5% (70) of the total number of mutations in the deafness related genes. The patients were 39, accounting for 10.89% of the total number, 18 GJB2235delc homozygous mutations, 3 homozygous mutations, 9 heterozygous mutations in del235c site and 9 in complex heterozygous mutations, 25% in 299delAT, 5.12% in 176del16, 74.33% in 235delC, 28 in SLC26A4, 7.82% in SLC26A4. The IVS7-2AG homozygous mutation was 4, the IVS7-2AG single heterozygous mutation was 20, the complex heterozygous mutation was 4. The mitochondrial DNAA1555G homozygous mutation was only 1, and the total number of 0.27%.GJB3 mutations was 2 of the total number 0.54%.. The subjects were divided into special and sporadic groups according to the different ways of visiting. The detection rate was 15.35% (37/241), the total detection rate of the sporadic group was 28.20% (33/117), and there were differences among the two groups, GJB2, SLC26A4, and mitochondrial DNA, and the detection rates of GJB3 gene mutations in the special group were (10.3%, 4.9%, 0,0), and the detection rates of the genes were (11.7%, 13.6%, 0.85%, 1.75%), and the mutation rate of GJB2 gene was not different P0.05 in the two groups. The mutation rate of SLC26A4 gene is different between the two and P0.01, which has statistical significance. Conclusion: the detection of deafness gene detection site and molecular diagnosis of deafness can provide a basis for prevention of deafness, marriage and breeding, guidance for rehabilitation and evaluation of prognosis. Environmental or other genetic factors play a role in the region.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R764.43
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