129例非综合征型耳聋患者耳聋基因的筛查

发布时间：2018-11-17 09:55

【摘要】：目的：应用基因检测芯片对非综合征型耳聋患者进行分子病因学的研究。为本地区制定及实施个性化的耳聋疾病防治政策提供理论指导。方法：收集太原市聋哑学校和山西医科大学第一附属医院门诊就诊的非综合征型耳聋患者，共计129人，采集外周血并从中提取DNA，应用耳聋基因芯片检测4个基因GJB2，GJB3，SLC26A4，线粒体DNA（mitochondrial，mtDNA）12SrRNA的热点突变位点，同时收集病人的一般情况、听力变动过程、加重或减轻的诱发因素、聋病史、家族史、是否使用耳毒性药物、头部是否受外伤等病史，行耳科常规检查、纯音测听、声导抗、听性脑干反应等听力学检查。对携带SLC26A4基因突变的患者进行回访，并行颞骨薄层高分辨率CT检查，以得到基因诊断与颞骨CT诊断的吻合率。获得该群体耳聋基因检测结果，采用遗传学标准判别分类，结合相应的病史、家族史、氨基糖甙类药物应用史，分析和探寻该耳聋人群中个体的真正发病原因，筛查出那部分患者是对药物敏感的个体，给予其明确的用药指导；筛查出那部分患者是颅内压增高易致听力下降的个体，给予正确的指导、干预、治疗，建议其避免感冒、头部外伤等因素的刺激。从而得到耳聋疾病预防和治疗方面的理论依据，运用于实际工作中，以期降低耳聋发病率。结果：该耳聋人群中与遗传因素有关的耳聋比例占41.09%（53/129），1.共检出GJB2基因突变26例（20.16%），其中235delC纯合突变9例，235delC单杂合突变8例，235delC和299-300delAT复合杂合突变1例，299-300delAT单杂合突变7例，，235delC和IVS7-2AG双杂合突变1例，未检测出176del16bp和35delG突变；2.线粒体基因1555A＞G均质性突变8例（6.20%），m.[1555AG]单杂合突变7例，双杂合突变1例：m.[1555AG]+c.[919-2AG]；3.共检出SLC26A4基因突变21例（16.28%），SLC26A4IVS7-2AG纯合突变7例，IVS7-2AG杂合突变11例，2168AG杂合突变3例；在该耳聋人群中未检出GJB3基因突变。结论：本次调查耳聋群体中遗传性聋比例高达41.09%，GJB2突变是该人群遗传性聋的最常见病因，SLC26A4突变为第二常见病因。本次调查的耳聋患者群体存在较高的遗传性聋发生率，特别是线粒体基因突变及SLC26A4发生率高于全国平均水平。
[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.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R764

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