129例非綜合征型耳聾患者耳聾基因的篩查
發(fā)布時間：2018-11-17 09:55
【摘要】：目的：應(yīng)用基因檢測芯片對非綜合征型耳聾患者進行分子病因?qū)W的研究。為本地區(qū)制定及實施個性化的耳聾疾病防治政策提供理論指導(dǎo)。 方法：收集太原市聾啞學(xué)校和山西醫(yī)科大學(xué)第一附屬醫(yī)院門診就診的非綜合征型耳聾患者，共計129人，采集外周血并從中提取DNA，應(yīng)用耳聾基因芯片檢測4個基因GJB2，GJB3，SLC26A4，線粒體DNA（mitochondrial，mtDNA）12SrRNA的熱點突變位點，同時收集病人的一般情況、聽力變動過程、加重或減輕的誘發(fā)因素、聾病史、家族史、是否使用耳毒性藥物、頭部是否受外傷等病史，行耳科常規(guī)檢查、純音測聽、聲導(dǎo)抗、聽性腦干反應(yīng)等聽力學(xué)檢查。對攜帶SLC26A4基因突變的患者進行回訪，并行顳骨薄層高分辨率CT檢查，以得到基因診斷與顳骨CT診斷的吻合率。獲得該群體耳聾基因檢測結(jié)果，采用遺傳學(xué)標(biāo)準(zhǔn)判別分類，結(jié)合相應(yīng)的病史、家族史、氨基糖甙類藥物應(yīng)用史，分析和探尋該耳聾人群中個體的真正發(fā)病原因，篩查出那部分患者是對藥物敏感的個體，給予其明確的用藥指導(dǎo)；篩查出那部分患者是顱內(nèi)壓增高易致聽力下降的個體，給予正確的指導(dǎo)、干預(yù)、治療，建議其避免感冒、頭部外傷等因素的刺激。從而得到耳聾疾病預(yù)防和治療方面的理論依據(jù)，運用于實際工作中，以期降低耳聾發(fā)病率。 結(jié)果：該耳聾人群中與遺傳因素有關(guān)的耳聾比例占41.09%（53/129），1.共檢出GJB2基因突變26例（20.16%），其中235delC純合突變9例，235delC單雜合突變8例，235delC和299-300delAT復(fù)合雜合突變1例，299-300delAT單雜合突變7例，，235delC和IVS7-2AG雙雜合突變1例，未檢測出176del16bp和35delG突變；2.線粒體基因1555A＞G均質(zhì)性突變8例（6.20%），m.[1555AG]單雜合突變7例，雙雜合突變1例：m.[1555AG]+c.[919-2AG]；3.共檢出SLC26A4基因突變21例（16.28%），SLC26A4IVS7-2AG純合突變7例，IVS7-2AG雜合突變11例，2168AG雜合突變3例；在該耳聾人群中未檢出GJB3基因突變。 結(jié)論：本次調(diào)查耳聾群體中遺傳性聾比例高達41.09%，GJB2突變是該人群遺傳性聾的最常見病因，SLC26A4突變?yōu)榈诙Ｒ姴∫�。本次調(diào)查的耳聾患者群體存在較高的遺傳性聾發(fā)生率，特別是線粒體基因突變及SLC26A4發(fā)生率高于全國平均水平。
[Abstract]:Objective: to study the molecular etiology of non-syndromic deafness by gene detection chip. To provide theoretical guidance for the development and implementation of personalized deaf disease prevention and treatment policy. Methods: a total of 129 non-syndromic deafness patients in Taiyuan Deaf-mute School and the first affiliated Hospital of Shanxi Medical University were collected. Peripheral blood samples were collected and DNA, was extracted from them to detect four GJB2,GJB3,SLC26A4, genes using deafness gene chip. The hot spot mutation site of mitochondrial DNA (mitochondrial,mtDNA) 12SrRNA was collected at the same time, the general condition of the patient, the process of hearing change, the inducing factors of aggravation or abatement, the history of deafness, the family history, the use of ototoxic drugs, whether the head was injured or not, etc. Routine otological examination, pure tone audiometry, acoustic impedance, auditory brainstem response and other audiological examination. The patients with SLC26A4 gene mutation were visited back, and thin slice high resolution CT examination of temporal bone was performed to obtain the coincidence rate between gene diagnosis and CT diagnosis of temporal bone. The genetic analysis and classification of the deafness gene in this population were carried out. Combining with the corresponding history, family history and the history of the application of aminoglycoside drugs, the authors analyzed and explored the real causes of the disease in the deafness population. Screening out that part of the patients are drug sensitive individuals, give their clear drug guidance; It is found that these patients are individuals who are prone to hearing loss due to increased intracranial pressure, and give them correct guidance, intervention, treatment and suggestions to avoid irritation caused by colds and head injuries. Thus, the theoretical basis of prevention and treatment of deafness is obtained and applied to practical work in order to reduce the incidence of deafness. Results: the proportion of deafness related to genetic factors was 41. 09% (53 / 129). A total of 26 (20.16%) cases of GJB2 gene mutations were detected, of which 9 were homozygous mutations of 235delC, 8 were single heterozygosity mutations of 235delC, 1 was combined heterozygosity mutation of 235delC and 299-300delAT, 7 were homozygous mutations of 299-300delAT, and 1 was double heterozygosity mutation of 235delC and IVS7-2AG. No 176del16bp and 35delG mutations were detected. 2. Mitochondrial gene 1555A > G homogeneity mutation was found in 8 cases (6.20%), m. [1555AG] single heterozygosity mutation in 7 cases and double heterozygosity mutation in 1 case: M. [1555AG] c. [919-2AG]; 3. There were 21 cases (16.28%) of SLC26A4 gene mutation, 7 cases of SLC26A4IVS7-2AG homozygous mutation, 11 cases of IVS7-2AG heterozygosity mutation and 3 cases of 2168AG heterozygosity mutation. Conclusion: GJB2 mutation is the most common cause of hereditary deafness and SLC26A4 mutation is the second most common cause of hereditary deafness. The incidence of hereditary deafness, especially mitochondrial gene mutation and SLC26A4, was higher than the national average.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R764
[Abstract]:Objective: to study the molecular etiology of non-syndromic deafness by gene detection chip. To provide theoretical guidance for the development and implementation of personalized deaf disease prevention and treatment policy. Methods: a total of 129 non-syndromic deafness patients in Taiyuan Deaf-mute School and the first affiliated Hospital of Shanxi Medical University were collected. Peripheral blood samples were collected and DNA, was extracted from them to detect four GJB2,GJB3,SLC26A4, genes using deafness gene chip. The hot spot mutation site of mitochondrial DNA (mitochondrial,mtDNA) 12SrRNA was collected at the same time, the general condition of the patient, the process of hearing change, the inducing factors of aggravation or abatement, the history of deafness, the family history, the use of ototoxic drugs, whether the head was injured or not, etc. Routine otological examination, pure tone audiometry, acoustic impedance, auditory brainstem response and other audiological examination. The patients with SLC26A4 gene mutation were visited back, and thin slice high resolution CT examination of temporal bone was performed to obtain the coincidence rate between gene diagnosis and CT diagnosis of temporal bone. The genetic analysis and classification of the deafness gene in this population were carried out. Combining with the corresponding history, family history and the history of the application of aminoglycoside drugs, the authors analyzed and explored the real causes of the disease in the deafness population. Screening out that part of the patients are drug sensitive individuals, give their clear drug guidance; It is found that these patients are individuals who are prone to hearing loss due to increased intracranial pressure, and give them correct guidance, intervention, treatment and suggestions to avoid irritation caused by colds and head injuries. Thus, the theoretical basis of prevention and treatment of deafness is obtained and applied to practical work in order to reduce the incidence of deafness. Results: the proportion of deafness related to genetic factors was 41. 09% (53 / 129). A total of 26 (20.16%) cases of GJB2 gene mutations were detected, of which 9 were homozygous mutations of 235delC, 8 were single heterozygosity mutations of 235delC, 1 was combined heterozygosity mutation of 235delC and 299-300delAT, 7 were homozygous mutations of 299-300delAT, and 1 was double heterozygosity mutation of 235delC and IVS7-2AG. No 176del16bp and 35delG mutations were detected. 2. Mitochondrial gene 1555A > G homogeneity mutation was found in 8 cases (6.20%), m. [1555AG] single heterozygosity mutation in 7 cases and double heterozygosity mutation in 1 case: M. [1555AG] c. [919-2AG]; 3. There were 21 cases (16.28%) of SLC26A4 gene mutation, 7 cases of SLC26A4IVS7-2AG homozygous mutation, 11 cases of IVS7-2AG heterozygosity mutation and 3 cases of 2168AG heterozygosity mutation. Conclusion: GJB2 mutation is the most common cause of hereditary deafness and SLC26A4 mutation is the second most common cause of hereditary deafness. The incidence of hereditary deafness, especially mitochondrial gene mutation and SLC26A4, was higher than the national average.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R764
【參考文獻】
相關(guān)期刊論文 前9條
1 王蘋,王新美,安秀芬,王宇聲,杜波,杜寶東;Connexin 26基因233delC突變與中國人先天性耳聾的研究[J];耳鼻咽喉頭頸外科;2001年01期
2 于飛,戴樸,韓東一;GJB2基因突變及語前遺傳性非綜合征性耳聾[J];國外醫(yī)學(xué).耳鼻咽喉科學(xué)分冊;2005年06期
3 柯肖枚,路遠(yuǎn),劉玉和,卜定方,朱平,戚豫,劉學(xué)忠;connexin 26基因突變與國人遺傳性無綜合征耳聾相關(guān)性分析[J];中華耳鼻咽喉科雜志;2001年03期
4 戴樸;朱秀輝;袁永一;朱慶文;滕國春;張昕;劉麗賢;王嘉陵;馮勃;翟所強;康東洋;劉新;黃德亮;;Pendred綜合征基因熱點突變篩查赤峰市聾啞學(xué)校大前庭水管綜合征患者[J];中華耳鼻咽喉頭頸外科雜志;2006年07期
5 鄭文波,羅建紅,酈云,余應(yīng)年,錢羽力;中國人語前非綜合征性耳聾患者GJB2基因的突變分析[J];中華兒科雜志;2000年10期
6 戴樸;劉新;于飛;朱慶文;袁永一;楊淑芝;孫R
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