先天性听力障碍婴幼儿颞骨影像学与聋病基因相关性研究

发布时间：2018-08-31 12:27

【摘要】：216例双侧听力障碍婴幼儿颞骨影像学与基因相关性研究目的：分析听力障碍婴幼儿常见致聋基因突变与颞骨影像学相关性。方法：2009年7月-2012年1月,收集上海及周边地区双侧听力障碍婴幼儿216例,采外周静脉血,利用PCR扩增目的基因后直接测序。对所有患儿进行常见致病基因GJB2全编码序列检测,SLC26A4.12SrRNA基因高发位点序列检测,应用Sequencher4.9软件对上述测序结果进行分析。对全部病例行颞骨CT检查,收集患儿临床听力学资料并随访。结果：216例双侧听力障碍患儿中,GJB2致病性突变19例(9%),SLC26A4致病性突变6例(3%),未发现12SrRNA1555A、1494C基因突变,颞骨CT提示解剖结构畸形者27例(12.5%),前庭导水管扩大不伴耳蜗畸形11例(5%)。GJB2基因79GA/235delC突变伴有双侧内听道缩窄。GJB2基因79GA,341AG和109GA纯合突变在轻、中度听力障碍患儿中较多。前庭导水管扩张的患儿中,SLC26A4基因7、8外显子剪切位点c.919-2AG突变为热点突变。结论：GJB2基因79GA,341AG和109GA纯合突变可能和轻、中度听力障碍有关。SLC26A4基因c.919-2AG突变与前庭导水管扩张有关。GJB2基因79GA/235delC突变可能与内听道畸形有关。 51例单侧听力障碍婴幼儿影像学及聋病基因突变研究分析目的：探讨先天性单侧听力障碍婴幼儿颞骨CT、常见致聋基因及临床听力学特征。方法：选取51例单侧听力障碍婴幼儿,平均年龄0.9岁,排除外耳畸形,抽取外周血提取基因组DNA,检测常见致聋基因GJB2、SLC26A4及线粒体12SrRNA1555A、1494C的突变。对全部病例行颞骨CT检查,收集患儿临床听力学资料并随访。结果：51例单侧听力障碍患儿中,32%(16/51)颞骨CT异常,其中3例中耳畸形,3例颈静脉球高位,4例前庭导水管扩张；发现1.9%(1/51)GJB2基因发生235delC/79GA,341AG致病突变,并伴有耳蜗不发育；4%(2/51)SLC26A4基因发生致病突变；未检测到12SrRNA1555A、1494C致聋突变。结论：单侧耳聋患者1/3都有影像学改变,其中颈静脉球高位发生率较高。GJB2和12SrRNA1555A、1494C基因突变在单侧听力障碍中发生率较低。单侧听力障碍患儿耳蜗畸形可能和GJB2基因突变有关。
[Abstract]:Imaging and Gene correlation of temporal Bone in 216 infants with bilateral hearing Disorder objective: to analyze the correlation between common deafness gene mutation and temporal bone imaging in infants with hearing impairment. Methods: from July 2009 to January 2012, 216 infants with bilateral hearing impairment were collected from Shanghai and its surrounding areas. Peripheral venous blood was collected. The target gene was amplified by PCR and sequenced directly. All the children were detected by GJB2 full coding sequence of common pathogenic gene SLC26A4.12SrRNA gene, and the results were analyzed by Sequencher4.9 software. Temporal bone CT was performed in all patients. Clinical audiological data were collected and followed up. Results among 216 children with bilateral hearing impairment, 19 (9%) had pathogenicity mutation of GJB2 and 6 (3%) had SLC26A4 pathogenicity mutation. No mutation of 12SrRNA1555An1494C gene was found. According to CT of temporal bone, 27 cases (12.5%) had anatomic structural malformation, 11 cases (5%) of vestibular aqueduct enlargement without cochlear malformation, 11 cases (5%) of 79GA/235delC mutation of GJB2 gene with bilateral constriction of auditory canal, 79GAJB2 gene 79GA341 AG and 109GA homozygous mutation were more common in children with mild and moderate hearing impairment. In children with vestibular aqueduct dilatation, the c.919-2AG mutation at exon 7 of SLC26A4 gene was a hot spot mutation. Conclusion the homozygous mutations of 79-GJB2 gene 79GAA341AG and 109GA may be mild. The c.919-2AG mutation of the. SLC26A4 gene is related to vestibular aqueduct dilatation. The 79GA/235delC mutation of the GJB2 gene may be related to the deformity of the internal auditory tract. Analysis of the genetic mutations in 51 infants with unilateral hearing impairment on imaging and deafness Objective: to investigate the common deafness genes and clinical audiological characteristics of CT, in infants with congenital unilateral hearing impairment. Methods: 51 infants with unilateral hearing impairment, with an average age of 0.9 years, were excluded from the deafness. Genomic DNA, was extracted from the peripheral blood to detect the mutations of common deafness gene GJB2,SLC26A4 and mitochondrial 12SrRNA1555Af1494C. Temporal bone CT was performed in all patients. Clinical audiological data were collected and followed up. Results among 51 children with unilateral hearing impairment, 32% (16 / 51) had abnormal CT in temporal bone, 3 cases of middle ear malformation, 3 cases of high jugular bulbar, 4 cases of dilatation of vestibular aqueduct, 1.9% (1 / 51) GJB2 gene was found to have 235del C / P 79 GA 341AG mutation and cochlear dysplasia. 4% (2 / 51) SLC26A4 gene was pathogenicity mutation, and no 12s rRNA 1555An 1494C deafness mutation was detected. Conclusion: one third of the patients with unilateral deafness have imaging changes, and the incidence of high level of jugular bulb is higher. GJB2 and 12s rRNA 1555Agna 1494C gene mutation is lower in unilateral hearing impairment. Cochlear malformation in children with unilateral hearing impairment may be related to mutation of GJB2 gene.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R764

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