Abstract:

Objective　To investigate the clinical significance of the clinical phenotype and gene mutation detection in children with Alport syndrome. Methods　The data of 30 children with gene mutation admitted to Guangzhou First People’s Hospital，Guangzhou Medical University from January 2013 to June 2017 were retrospectively analyzed. Collect peripheral blood samples from children and their family members .Then use gene sequencing exon sequence capture technology to find out whether there was mutation gene，including Ⅳ type collagen alpha 3 chain（COL4A3），alpha 4 chain（COL4A4） or alpha 5 chain（COL4A5）. Gene mutations of related family members were identified by Sanger method. Results　The 30 children with AS were diagnosed by gene detection. Renal biopsy was performed in 18 cases（60.00%） of 30 children with AS，and the results of light microscopy were various. Electron microscopic examination revealed diffuse thinning，thickening and delamination of the glomerular basement membrane（GBM） in 5 cases（16.67%）. The electron microscopic examination showed thin basement membrane disease in 4 cases（13.33%）. Three cases（10.00%） of immunofluorescence showed type Ⅳ collagen alpha 3，alpha 5 chain negative in renal tissue. Totally 22 cases were diagnosed with X linkage dominant hereditary Alport syndrome（XL-AS） by gene text，and 8 new mutation sites of COL4A5 were found. Genetic diagnosis showed 8 children were autosomal recessive inheritance，and 3 new COL4A4 mutations were found. Conclusion　The clinical manifestations of children with Alport syndrome are diverse and lack of specificity，and the pathological types of renal tissue are different. It is difficult to diagnose early. Gene detection helps to early diagnose of AS，to judge the prognosis of the children，and to avoid unnecessary drug treatment.

Key words: Alport syndrome, gene diagnosis, type IV collagen, child

摘要：

目的　探讨儿童Alport综合征（Alport syndrome，AS）的临床表型与基因突变检测的临床意义。方法　回顾性分析2013年1月至2017年6月在广州医科大学附属广州市第一人民医院儿科收治的30例基因突变患儿的资料。采集患儿及其家系成员的外周血样品，应用基因测序外显子序列捕获技术，寻找样品中是否存在Ⅳ型胶原α3链（COL4A3）、α4链（COL4A4）或α5链（COL4A5）三个突变基因，并对直系亲属行基因验证。结果　经过基因检测确诊Alport综合征（AS）30例，18例（60.00%）进行肾活检，光镜检查结果呈多样化，5例（16.67%）电镜检查表现为肾小球基底膜（glomerularbasementmembrane，GBM）弥漫性变薄、增厚和撕裂分层； 4例（13.33%）电镜表现为薄基底膜病（thin basement membrane nephropathy，TBMN）改变；免疫荧光检查3例（10.00%）肾组织Ⅳ型胶原α3、α5链阴性。22例患儿基因诊断X连锁显性遗传Alport syndrome （X-linked Alport syndrome，XL-AS），发现8个COL4A5新突变位点。8例患儿基因诊断为常染色体隐性遗传（autosomal recessive Alport Syndrome，AR-AS），发现3个COL4A4新突变位点。结论　儿童Alport综合征临床表现多样化，缺乏特异性，肾组织病理类型各异，难以早期诊断。基因检测有助于AS的早期诊断，判断患儿的预后，避免不必要的药物治疗。

关键词: Alport综合征, 基因诊断, IV型胶原, 儿童