先证者诊断为IgA肾病的三个家族性血尿家系血尿相关基因变异  

Genetic variants of familial hematuria associated genes in three families with hematuria with probands initially diagnosed as IgA nephropathy

作　　者：刘洁玮 王萍 黄隽 聂晓晶 赵锋 陈丽珠 李政 余自华 Liu Jiewei;Wang Ping;Huang Jun;Nie Xiaojing;Zhao Feng;Chen Lizhu;Li Zheng;Yu Zihua(Department of Pediatrics, Fuzhou Clinical Medical College, Naval Medical University, Fuzhou 350025, China;Department of Pediatrics, the 900th Hospital of Joint Logistic Support Force, the People′s Liberation Army, Fuzhou 350025, China)

机构地区：[1]海军军医大学福州临床医学院儿科,350025 [2]解放军联勤保障部队第九〇〇医院儿科,福州350025

出　　处：《中华儿科杂志》2019年第9期674-679,共6页Chinese Journal of Pediatrics

基　　金：国家自然科学基金(81270766);福建省社会发展重点课题(2013Y0072);南京军区重大科研课题(14ZX27).

摘　　要：目的分析先证者诊断为IgA肾病的3个家族性血尿家系的血尿相关基因变异。方法回顾性分析原南京军区福州总医院儿科2014年8月至2018年5月收治的3个家族性血尿家系中的3例血尿患儿及先证者的临床资料、实验室检查和家系基因检测结果。结果家系1先证者(男,8岁)临床表现为肉眼血尿,肾活检病理提示IgA肾病;其父亲(44岁)临床也表现为血尿。基因检测提示先证者及其父亲CFHR5基因533A>G(Asn178Ser)杂合变异。家系2患儿(女,4岁)临床表现为血尿;患儿父亲(36岁,先证者)临床表现为血尿蛋白尿、高频感音神经性耳聋、肾功能不全,在无肾活检组织电镜检查、肾组织Ⅳ型胶原α3、α4、α5链免疫荧光和皮肤Ⅳ型胶原α5链免疫荧光检查情况下,根据临床表现、肾脏病理光镜和常规免疫组化检查诊断为IgA肾病。基因检测提示患儿及其父亲COL4A5基因566G>T(Gly189Val)杂合或半合子变异。家系3患儿(女,7岁)临床表现为血尿蛋白尿;患儿母亲(34岁,先证者)临床也表现为血尿蛋白尿。用家系2同样的方法,患儿母亲也诊断为IgA肾病。患儿外祖父44岁死于"尿毒症"。基因检测提示患儿及其母亲COL4A5基因539G>A(Gly180Glu)杂合变异。结论家系1先证者CFHR5基因变异致病性不明确,家系2、3先证者COL4A5基因变异致病,后2位先证者确诊为Alport综合征,提示临床医生对仅根据临床表现、肾脏病理光镜和常规免疫组化检查而诊断先证者为IgA肾病的家族性血尿家系需进行家族性血尿相关基因检测。Objective To examine genetic variants of familial hematuria (FH) associated genes in 3 families with hematuria with probands initially diagnosed with IgA nephropathy (IgAN). Methods A retrospective analysis was performed on the clinical data, laboratory tests and genetic test results of three children with hematuria and the probands in three families with hematuria. The families were ascertained at the Department of Pediatrics, Fuzhou General Hospital of Nanjing Military Command from August 2014 to May 2018. Results The proband of Family One, an 8-year-old boy, manifested gross hematuria. His renal biopsy pathology revealed IgAN. His father also manifested hematuria. Genetic testing showed that the proband and his father carried a heterozygous variant of the CFHR5 gene,533A>G (Asn178Ser). The child of Family Two, a 4-year-old girl, manifested hematuria. Her father, the proband of the family, was 36 years old, and manifested hematuria, proteinuria, high-frequency sensorineural deafness and renal insufficiency. He was diagnosed as IgAN according to clinical manifestations, renal pathology and routine immunohistochemistry without renal biopsy electron microscopy, renal tissue type Ⅳ collagen α3,α4,α5 chains immunofluorescence and skin type Ⅳ collagen α5 chain immunofluorescence. Genetic testing showed that the girl carried a heterozygous variant of the COL4A5 gene,566G>T (Gly189Val), and her father carried the hemizygous variant. The child of Family Three, a 7-year-old girl, manifested hematuria and proteinuria. Her mother, the proband of the family, was 34 years old, and manifested hematuria and proteinuria as well. The proband was diagnosed as IgAN by the same method used for Family Two. The girl′s grandfather died of uremia at the age of 44. Genetic testing showed that the girl and her mother carried a heterozygous variant 539G>A (Gly180Glu)in COL4A5 gene. Conclusions The variant of the CFHR5 gene identified in Family One is of uncertain signifance, and the two variants of the COL4A5 gene identified in

关 键 词：血尿 肾小球肾炎 IGA 肾炎 遗传性 

分 类 号：R726.9[医药卫生—儿科] R692.31[医药卫生—临床医学]