X连锁Alport综合征女性患者的临床听力学特征及与基因型的关系  

X-linked Alport syndrome:auditory pathogenic variant features and further genotype-phenotype correlations in female patients

作　　者：张晓[1] 张琰琴[2] 张燕梅[1] 顾红波[1] 陈喆 任蕾 卢星星 陈丽[1] 王芳[2] 刘玉和[1] 丁洁[2] ZHANG Xiao;ZHANG Yanqin;ZHANG Yanmei;GU Hongbo;CHEN Zhe;REN Lei;LU Xingxing;CHEN Li;WANG Fang;LIU Yuhe;DING Jie(Department of Otolaryngology Head and Neck Surgery,Peking University First Hospital,Beijing,100034,China;Department of Pediatrics,Peking University First Hospital)

机构地区：[1]北京大学第一医院耳鼻咽喉头颈外科,北京100034 [2]北京大学第一医院儿科

出　　处：《临床耳鼻咽喉头颈外科杂志》2018年第16期1232-1237,共6页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

基　　金：国家自然科学基金面上项目(No:81271083;81470691);国家重点研发计划精准医学研究重点专项课题(No:2016YFC 0901505);儿科遗传性疾病分子诊断与研究北京市重点实验室(No:BZ0317)

摘　　要：目的:分析国人X连锁Alport综合征女性患者的临床听力学特点,并探讨其听力表型与基因型之间的关系。方法:总结64例X连锁Alport综合征女性患者的临床资料,对主要临床听力学表现进行回顾性分析,并采用检测皮肤成纤维细胞mRNA的方法或外周血DNA扩增直接测序的方法对患者进行IV型胶原α5链基因的检测。按照突变类型分为轻型突变和重型突变,并进行临床表型和基因型关系分析。结果:64例女性患者均有血尿或蛋白尿,均行纯音测听、声导抗检查,其中听力正常者51例,听力下降者13例,均表现为轻度或中度双侧对称性感音神经性聋,均以中频听力下降为主,听力曲线为槽型。64例患者中52例检测出COL4A5基因突变,共检出42种突变。听力损失患者中,除1例12岁外,其余均≥35岁。25例≥35岁患者中,轻型突变13例(10例听力正常,3例听力轻度下降),重型突变12例(6例听力正常,6例听力轻中度下降)。随访≥2年者26例,其中7例听力呈下降趋势,均为随访2年者,每年下降约5dB,余听力无明显变化。结论:国人X连锁Alport综合征女性患者,早年出现血尿或蛋白尿,多于中年后开始出现迟发进展性听力损失,多为轻中度,曲线为槽型;听力损失发生时间较男性患者晚,并且听力损失严重程度较男性轻;听力表型与基因型之间未发现明显相关性。Objective：To analyze the audiological characteristics of female patients with X-linked Alport syndrome and to explore the relationship between genotype and phenotype in China.Method：The hearing data of 64 females diagnosed as Alport syndrome was reviewed and analyzed.All coding exons of COL4A5 genes were PCRamplified and sequenced with genomic DNA,or mRNA of COL4A5 gene was RT-PCR amplified and sequenced with skin fibroblast.Result：The 64 cases who were accompanied by hematuria or proteinuria all received pure tone audiometry and acoustic immitance test.The incidence of hearing loss was 20.31%（13/64）.The hearing were bilaterally symmetrical sensorineural deafness,most of which were mild and moderate hearing loss.The hearing curve is the groove curve.Among the 64 patients,42 kinds of DNA variants were detected in 52 cases.Among the patients with hearing loss,1 of them was 12 years old and the rest were over 35 years old.Mild mutations in 13 cases（10 cases of normal hearing and 3 cases of mild hearing loss）and severe mutations in in 12 cases（6 cases of normal hearing and 6 cases of mild to moderate hearing loss）were found in 25 cases over 35 years old.A total of 26 cases were followed up for 2 years or more,of which 7 cases had a downward trend of hearing loss,decreased about 5 dB each year,and there was no significant change in the hearing of the other patients.Conclusion：Mild and moderate hearing impairment,and groove type of audiometric curve are mainly found in Chinese X-linked Alport syndrome in females.Hearing loss occurs at middle-age.The onset time of hearing loss was later than that of the male,and the severity of hearing loss was lighter than that of the male.In the course of follow-up,some patients had a downward trend in hearing,and there was no significant correlation between the hearing phenotype and the genotype.

关 键 词：ALPORT综合征 女性 听力学特征 基因突变 聋 

分 类 号：R764[医药卫生—耳鼻咽喉科]