儿童Alport综合征1例COL4A5基因新发突变分析

Analysis of a novel mutation of COL4A5 gene in a child with Alport syndrome

目的分析儿童Alport综合征的基因型和临床特点。方法回顾分析1例Alport综合征患儿的临床资料及基因检测结果。结果患儿男性,11岁,7岁出现不明原因的血尿、蛋白尿,肾功能轻度异常,因治疗依从性差而进展至慢性肾脏病尿毒症期。肾穿刺活检病理显示,慢性硬化性肾小球病变,弥漫性肾小管萎缩(萎缩面积超80%);免疫荧光染色α3、α5(IV)基底膜染色阳性。基因检测显示,COL4A5基因存在的一处半合子突变c.2631dupA(插入突变),导致氨基酸改变p.G 878 Rfs*20(移码突变20位后蛋白翻译提前终止);家系验证其为新发突变,父母均未携带。依据ACMG指南,该突变变异类型为致病性突变。查阅HGMDpro数据库未见报道。结论基因检测有助于确诊Alport综合征,新发现COL4A5基因半合子突变。

Objective To analyze the genotype and clinical characteristics of Alport syndrome in children.Methods Clinical manifestation and genetic test results of 1 Chinese boy with Alport syndrome were retrospectively analyzed.Results The 11-year-old male patient presented with unexplained hematuria and proteinuria with mild renal dysfunction 4 years ago and progressed to the uremia stage of chronic kidney disease due to poor treatment compliance.There was no high-frequency hearing impairment and ocular fundus pathology.Renal biopsy showed chronic sclerosing glomerular disease and diffuse tubular atrophy(atrophy area over 80%).Immunofluorescence staining of basement membrane of alpha 3 and alpha 5(IV)were positive.Gene sequencing identified a hemizygous mutation of c.2631dupA(insertion)in COL4A5 gene,resulted in amino acid changes of p.G878Rfs*20(prematurely termination of protein translation after 20 amino acids).It was identified as a de novo mutation.According to ACMG guidelines.This variant is classified as pathogenic.It has not been reported in the HGMDpro database.Conclusion Gene sequencing is helpful for the diagnosis of Alport syndrome and the discovery of novel variant of COL4A5 gene.