Waardenburg综合征的分子遗传学、内耳畸形及其人工耳蜗植入效果的研究

发布时间：2018-05-09 10:19

本文选题：Waardenburg综合征 + 内耳畸形　；参考：《中国人民解放军医学院》2014年硕士论文

【摘要】：Waardenburg综合征(Waardenburg syndrome，WS)是一种较少见的遗传性听力-色素异常综合症，临床表现主要为感音神经性耳聋、早白发或额前白发、虹膜异色、皮肤色素异常、内眦异位等。WS根据其临床表现分为4型，， WS1型与WS2型在我国较多见。目前发现的与WS1及WS2明确相关的致病基因有：PAX3及MITF、SOX10。研究探讨WS的分子遗传学特征，了解各基因功的能提，可以提高WS患者的基因诊断率、产前筛查率；分析WS患者内耳影像学的特点，探讨基因型与内耳畸形之间的相关性，并对其人工耳蜗植入术后的听觉言语康复水平进行评估，可以为WS患者手术前评估、植入电极的选择提供参考，对于提高WS患者听觉言语水平及生活质量，具有重要意义。收集来301医院耳鼻咽喉头颈外科就诊，根据临床表现明确诊断为WS1的双耳极重度感音神经性耳聋患者1例、诊断为WS2的极重度感音神经性耳聋患者16例；其中在我科行人工耳蜗植入术的WS1患者1例、WS2患者14例。对所有17例WS患者，均行颞骨高分辨率CT、磁共振内耳三维重建检查；对所有17例WS患者进行PAX3、MITF、SOX10基因编码区的全部外显子测序；并对15例行人工耳蜗植入术后的WS患者的听觉言语康复效果进行评估。 17例WS患者，共筛查出8例致病突变，其中5例为新发现的致病突变、3例为已报道的致病突变。携带MITF基因突变的3例WS2患者及携带PAX3基因突变的1例WS1患者，影像学检查基本正常；携带SOX10致病突变的4例WS2患者，影像学检查表现为双侧内耳畸形，其中未筛出致病突变的3例患者也表现为双侧内耳畸形。所有15例患者术中均插入电极顺利，术后言语康复效果均较佳。
[Abstract]:Waardenburg syndrome (Waardenburg syndrome) is a rare hereditary hearing pigmentation syndrome. Its clinical manifestations are sensorineural deafness, early white hair or prefrontal white hair, iris discoloration and abnormal skin pigmentation. According to the clinical manifestations of ectopic canthus, WS can be divided into 4 types, WS1 type and WS2 type are more common in China. The pathogenicity genes associated with WS1 and WS2 are: PAX3 and MITFSOX10. To study the molecular genetic characteristics of WS, to understand the ability of gene work, to improve the rate of gene diagnosis and prenatal screening in WS patients, to analyze the imaging features of the inner ear of WS patients, and to explore the correlation between genotype and inner ear malformation. The evaluation of the level of auditory speech rehabilitation after cochlear implantation can provide a reference for the pre-operation evaluation and the selection of implanted electrodes in WS patients. It is of great significance to improve the auditory speech level and the quality of life of WS patients. According to clinical manifestations, 1 patient with WS1 and 16 patients with very severe sensorineural deafness diagnosed as WS2 were collected from head and neck surgery of otolaryngology and larynx in 301 Hospital. Cochlear implants were performed in our department. There were 14 cases of WS1 and 14 cases of WS2. All 17 cases of WS were examined by high resolution CTS and 3D reconstruction of inner ear of temporal bone, and all 17 cases of WS were sequenced all exon of PAX3 mite MITFSOX10 gene coding region. The effects of auditory and verbal rehabilitation of 15 WS patients after cochlear implantation were evaluated. Among the 17 WS patients, 8 cases were screened out, among which 5 cases were newly found mutations and 3 cases were reported mutations. Three WS2 patients with MITF gene mutation and one WS1 patient with PAX3 gene mutation had normal imaging examination, and 4 WS2 patients with SOX10 pathogenicity mutation showed bilateral inner ear malformation. Among them, 3 patients with no mutation were also presented with bilateral inner ear malformation. All the 15 patients were successfully inserted into the electrode during operation, and the effect of speech rehabilitation was better after operation.
【学位授予单位】：中国人民解放军医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R764.9

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