本文選題：耳聾 + GJB2基因��； 參考：《青島大學(xué)》2017年碩士論文

【摘要】：目的:探討運用基因芯片和DNA測序技術(shù)檢測非綜合征型耳聾(non-syndromic hearing loss,NSHL)患者的基因突變類型的臨床應(yīng)用價值。方法:收集并分析患者一般情況、聽力變動過程、加重或減輕的誘發(fā)因素、聾病史、家族史,檢查全身情況以排除綜合征型耳聾。采集非綜合征型耳聾患者和健康體檢者靜脈血標(biāo)本,提取DNA并進行PCR擴增,運用耳聾基因芯片技術(shù)確診患者基因的突變類型,同時運用DNA測序方法進行結(jié)果驗證。綜合性分析我國各地區(qū)非綜合征型耳聾患者的GJB2基因突變位點,研究對比不同實驗中患者納入標(biāo)準、檢測技術(shù)、實驗數(shù)據(jù)之間差異性,制定我國統(tǒng)一的耳聾基因流行病學(xué)調(diào)查的規(guī)范化標(biāo)準。選取健康體檢者聽力檢測正常、沒有遺傳性聽力下降家族史的體格正常的人群作為正常對照。結(jié)果:遺傳性耳聾主要是指基因異常所致的耳聾,是人類最常見的感覺神經(jīng)系統(tǒng)缺陷。這種疾病通過常染色體隱性,常染色體顯性,X-連鎖遺傳和線粒體遺傳方式遺傳給下一代。在遺傳性耳聾中,30%伴其他癥狀,稱為綜合征型耳聾;70%不伴其他癥狀,稱為非綜合征型耳聾(non-syndromic hearing loss,NSHL)。在GJB2(35del G、176dell6、235del C及299del AT)、GJB3(538CT)、SLC26A4(IVS7—2AG、2168AG)和線粒體DNA12Sr RNA(1555AG、C1494CT)這9個與非綜合征型耳聾相關(guān)的基因位點中,檢出GJB2基因235 del位點出現(xiàn)純合突變,基因芯片的結(jié)果與測序結(jié)果完全一致,健康對照者中所有結(jié)果均為陰性;同時研究認為:NSHL患者人群中,GJB2基因編碼區(qū)序列上共發(fā)現(xiàn)23種核苷酸改變,包括:5個框架移碼突變、1個無義突變、15個錯義突變及2個同義突變。GJB2基因突變在亞洲人遺傳性耳聾中也有較高的攜帶比例,在中國人群的調(diào)查中,GJB2基因突變的主要方式為235de1C,是我國非綜合征型耳聾人群中突最重要的致聾因素之一。結(jié)論:該非綜合征型耳聾患者存在GJB2基因235 del位點純合突變,且與擴增GJB2基因并進行DNA測序突變結(jié)果完全一致,基因芯片技術(shù)有助于診斷非綜合征型耳聾。耳聾基因芯片法檢測此類疾病,且聯(lián)合分子流行病學(xué)調(diào)查以及通過產(chǎn)前基因診斷進行生育指導(dǎo)和干預(yù)均具有重要的臨床意義。
[Abstract]:Objective: to investigate the clinical application value of gene mutation type in non-syndromic hearing (NHL) patients with non-syndromic deafness by gene chip and DNA sequencing.Methods: to collect and analyze the general situation of the patients, the process of hearing change, the aggravating or mitigating factors, the history of deafness, the family history, and to check the whole body condition to exclude the syndromic deafness.DNA was extracted from venous blood samples from non-syndromic deafness patients and healthy controls. The mutation type of genes was confirmed by using deafness gene chip technology. The results were verified by DNA sequencing method.The mutation sites of GJB2 gene in non-syndromic deafness patients in different regions of China were comprehensively analyzed, and the differences among the patient inclusion criteria, detection techniques and experimental data in different experiments were studied and compared.To establish a standardized standard for genetic epidemiological investigation of deafness in China.The healthy subjects with normal hearing test and no family history of hereditary hearing loss were selected as normal controls.Results: hereditary deafness mainly refers to deafness caused by genetic abnormality, which is the most common defect of human sensory nervous system.The disease is inherited to the next generation by autosomal recessive, autosomal dominant X-linkage and mitochondrial inheritance.30% of hereditary deafness were associated with other symptoms, 70% of which were called syndromic deafness without other symptoms, and were called non-syndromic hearing loss.All the results were negative in healthy controls and 23 nucleotide changes were found in the coding region of the GJB2 gene in the population with 1: NSHL.Among them, 5 frameshift mutations, 1 nonsense mutation, 15 missense mutations and 2 synonymous mutations. GJB2 gene mutations also have a high proportion of carriers in hereditary deafness in Asia.The main mutation pattern of GJB2 gene in Chinese population is 235de1C, which is one of the most important causes of deafness in non-syndromic deafness population in China.Conclusion: there is a homozygous mutation at the 235 del site of GJB2 gene in this non-syndromic deafness patient, which is consistent with the results of amplification of GJB2 gene and DNA sequencing. Gene chip technique is helpful for the diagnosis of non-syndromic deafness.It is of great clinical significance to detect the deafness disease by microarray method and to combine the molecular epidemiology investigation and prenatal gene diagnosis to guide and intervene the deafness disease.
【學(xué)位授予單位】：青島大學(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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