X连锁显性遗传型Alport肾病综合征患儿1例的临床及遗传学分析  

Clinical and genetic analysis of a child with X-linked dominant Alport syndrome

作　　者：常甜 韩智 刘肖 王盼盼[4] Chang Tian;Han Zhi;Liu Xiao;Wang Panpan(Department of Nephrology of Integrated Traditional Chinese and Western Medicine,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China;Blood Purification Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China;Cerebrovascular Surgery Ward 1,Henan Provincial People′s Hospital,Zhengzhou,Henan 4500052,China;School of Nursing,Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院中西医结合肾病科,郑州450052 [2]郑州大学第一附属医院血液净化中心,郑州450052 [3]河南省人民医院脑血管一病区,郑州450052 [4]郑州大学护理学院,郑州450052

出　　处：《中华医学遗传学杂志》2023年第10期1270-1274,共5页Chinese Journal of Medical Genetics

基　　金：河南省科技攻关计划(212102310767)。

摘　　要：目的探讨1例X连锁显性遗传Alport综合征(XLAS)患儿的临床特征及基因变异特点。方法选取2019年5月至郑州大学第一附属医院肾内科就诊的1例XLAS患儿为研究对象。收集患儿的临床资料。应用二代测序(NGS)对患者进行基因检测,针对候选致病变异,进行Sanger测序家系验证。结果患为12岁男性,儿主要临床表现为肉眼血尿、蛋白尿、肾病综合征,呈渐进性肾损害,伴听力下降,肾穿刺病理活组织检查提示肾小球基底膜弥散厚薄不均。基因检测结果提示患儿及其母亲携带COL4A5基因c.2632G>A(p.G878R)半合子变异,其父亲及弟弟该位点为野生型。该变异既往未见报道,根据美国医学遗传学和基因组学学会相关指南评估为致病性变异(PS1+PM1+PM2_Supporting+PP3)结论母源性COL4A5基因c.2632G>A(p.G878R)变异可能为该XLAS患儿的遗传学病因。本研究丰富了COL4A5基因的变异谱。Objective To investigate the clinical features and genetic variant of a child with X-linked dominant Alport syndrome(XLAS).Methods A child who had presented at the First Affiliated Hospital of Zhengzhou University in May 2019 was selected as the study subject.Clinical data of the child was collected.Next generation sequencing(NGS)was carried out for the child.Candidate variants were validated by Sanger sequencing of his family members.Results The child,a 12-year-old boy,had mainly manifested gross hematuria,proteinuria,nephrotic syndrome,and progressive renal impairment in conjunct with hearing loss.Kidney biopsy has revealed uneven glomerular basement membrane thickness.DNA sequencing revealed that the child and his mother have both carried a heterozygous c.2632G>A(p.G878R)variant of the COL4A5 gene,for which his father and brother were of the wild type.This variant was unreported previously.Based on the guidelines from the American College of Medical Genetics and Genomics,the variant was classified as pathogenic(PS1+PM1+PM2_Supporting+PP3).Conclusion The maternally derived hemizygous c.2632G>A(p.G878R)variant of the COL4A5 gene probably underlay the XLAS in this child.Above finding has enriched the mutational spectrum of the COL4A5 gene.

关 键 词：ALPORT综合征 X连锁显性遗传 COL4A5基因 基因变异 

分 类 号：R726.9[医药卫生—儿科]