单中心儿童Alport综合征基因型与临床表型特点分析

Features of clinical phenotype and genotype in children with Alport syndrome in a single-center study

摘要:

目的：了解儿童Alport综合征（Alport syndrome，AS）基因型与临床表型的特点。方法：收集我科2013年5月至2017年5月28例AS患儿的临床及实验室资料、肾活检、基因检测结果等资料，回顾性分析其基因型及临床表型的特点。结果：本组资料中Alport综合征X连锁显性遗传（X-linked Alport syndrome，XLAS）21例，常染色体隐性遗传（autosomal recessive inheritance，ARAS）1例，常染色体显性遗传（autosomal dominant inheritance，ADAS）4例，XLAS合并ADAS 2例。28例以血尿为首发表现，2例有听力损害，3例有眼部病变，5例有肾功能损害。家族史阳性者23例。17例行肾活检，仅4例为AS典型电镜病理表现；16例行免疫荧光检测，仅5例α3、α5链表达缺失。本组资料共发现34个突变位点，错义突变25个，移码突变4个，剪切突变3个，终止突变2个，大片段缺失1个，其中24个基因突变位点未见报道。结论：AS以X连锁显性遗传多见，致病性突变以错义突变为主。血尿为最常见临床表型，可伴或不伴蛋白尿，肾外表现少见。AS患儿肾脏病理多表现为肾小球轻微病变，电镜表现常不典型，漏诊率高，基因检测是AS诊断的重要手段。

Abstract:

Objective：To investigate the features of clinical phenotype and genotype in children with Alport syndrome（AS）. Methods：The clinical and laboratory data，renal biopsy results，and gene detection results of 28 children with AS who were treated in our de－partment from May 2013 to May 2017 were collected，and a retrospective analysis was performed to investigate the features of clinical phenotype and genotype. Results：Of all 28 children，21 had X-linked Alport syndrome（XLAS），1 had autosomal recessive Alport syndrome，4 had autosomal dominant Alport syndrome（ADAS），and 2 had XLAS and ADAS. All 28 children had hematuria as the initial manifestation；2 had hearing impairment，3 had ocular lesions，and 5 had renal dysfunction. Of all children，23 had a positive family history. Renal biopsy was performed for 17 children，among whom only 4 had typical pathological manifestations of AS under an electron microscope；immunofluorescence assay was performed for 16 children，among whom only 5 had absent expression of α3 and α5 chains. A total of 34 mutation sites were found，with 25 missense mutations，4 frameshift mutations，3 shear mutations，2 stop mutations，and 1 large fragment deletion，and 24 mutation sites had not been reported before. Conclusion：XLAS is the most common type of AS and missense mutation is the main type of pathogenic mutation. Hematuria is the most common clinical manifestation，with or without proteinuria，and extrarenal manifestations are rare. Renal biopsy shows minimal change disease in most children with AS，with atypical findings under an electron microscope，which leads to a high rate of missed diagnosis. Gene detection is an important method for the diagnosis of AS.