儿童Alport综合征COL4A5基因4种新突变分析  

Analysis of 4 novel mutations of COL4A5 gene in children with Alport syndrome

作　　者：都娟[1] 黄建萍[1] 赵晓艳[1] 王硕[1] 肖丽丽[1] 张尼娜 

机构地区：[1]北京军区总医院附属八一儿童医院肾病和免疫科,北京100700 [2]深圳华大基因健康科技有限公司,深圳518083

出　　处：《中国循证儿科杂志》2013年第1期27-30,共4页Chinese Journal of Evidence Based Pediatrics

摘　　要：目的分析4例儿童Alport综合征的基因型和临床表型特点。方法总结4例患儿的临床特点,采用外显子捕获-第二代测序技术对4例诊断为Alport综合征患儿的COL4A5、COL4A4和COL4A3基因进行突变检测。结果 4例均为男性,年龄6～8岁,首发症状均为血尿,均伴有不同程度的蛋白尿。1例表现为高频听力区受损,1例右侧视网膜脱色素改变。4例肾功能均正常。肾穿刺活检电镜检查均显示典型Alport综合征基底膜病变。在4个家系中发现4种COL4A5基因突变,分别为Gly132Glu、Gly1238Arg、Gly267Arg和Gly1033Ser,均为未报道的新突变。经家系验证Gly132Glu和Gly1033Ser为新生突变。用SIFT和PolyPhen软件进行蛋白功能预测均显示4种突变为有害突变。结论本研究采用外显子捕获-第二代测序技术共检测到4种COL4A5基因新突变,其中2种为新生突变。为人类Alport综合征基因突变数据库增添了4个新成员,对进一步研究中国人群Alport综合征的发病机制以及遗传咨询和产前诊断有重大意义。Objective To analyze the clinical features and gene mutation of 4 Chinese children with Alport syndrome. Methods The clinical and laboratory data of 4 chiidren with Alport syndrome were summarized. COIAA5, COIAA4 and COL4A3 genes were analyzed using next-generation sequencing. Results Four patients all presented an atypical clinical picture with onset of hematuria accompanied with different degrees of proteinuria . Ophthalmology, otolaryngology and renal function studies showed no abnormalities, except for a sensorineural hearing loss detected in case 2. Characteristic uhrastructual changes of the glomerular basement membrane were found in all patients. Four pathogenic mutations were identified in COL4A5 gene in the 4 families, including Gly132Glu, Gly1238Arg, Gly267Arg and Gly1033Ser. The 4 mutations were not reported previously, two of which were the novel mutations. Conclusions The 4 novel mutations in coding DNA of COL4A5 gene identified in our study contribute to further study of pathogenesis of Alport syndrome , ~enetic counsellinz and prenatal diaznosis in Chinese poPulation.

关 键 词：基因突变 儿童 ALPORT综合征 COL4A5 第二代测序技术 

分 类 号：R450[医药卫生—治疗学]