Liu J W, Wang P, Huang J, Nie X J, Zhao F, Chen L Z, Li Z, Yu Z H
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.
Zhonghua Er Ke Za Zhi. 2019 Sep 2;57(9):674-679. doi: 10.3760/cma.j.issn.0578-1310.2019.09.006.
To examine genetic variants of familial hematuria (FH) associated genes in 3 families with hematuria with probands initially diagnosed with IgA nephropathy (IgAN). 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. 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. The variant of the CFHR5 gene identified in Family One is of uncertain signifance, and the two variants of the COL4A5 gene identified in Families Two and Three are pathogenic. The probands of Families Two and Three are diagnosed as Alport syndrome. The study suggests that clinicians should examine genetic variants of FH associated genes in families with hematuria when the probands were diagnosed as IgAN by their clinical manifestations, renal pathology and routine immunohistochemistry.
为检测3个血尿家族中最初被诊断为IgA肾病（IgAN）的先证者的家族性血尿（FH）相关基因的遗传变异。对3个血尿患儿及3个血尿家族的先证者的临床资料、实验室检查和基因检测结果进行回顾性分析。这些家族于2014年8月至2018年5月在南京军区福州总医院儿科确诊。家族一的先证者是一名8岁男孩，表现为肉眼血尿。其肾活检病理显示为IgAN。他的父亲也有血尿表现。基因检测显示先证者及其父亲携带CFHR5基因的杂合变异，533A>G（Asn178Ser）。家族二的患儿是一名4岁女孩，有血尿表现。她的父亲，即该家族的先证者，36岁，有血尿、蛋白尿、高频感音神经性耳聋和肾功能不全。根据临床表现、肾脏病理和常规免疫组化，在未进行肾活检电镜、肾组织Ⅳ型胶原α3、α4、α5链免疫荧光及皮肤Ⅳ型胶原α5链免疫荧光检查的情况下，他被诊断为IgAN。基因检测显示该女孩携带COL4A5基因的杂合变异，566G>T（Gly189Val），其父亲携带半合子变异。家族三的患儿是一名7岁女孩，有血尿和蛋白尿表现。她的母亲，即该家族的先证者，34岁，也有血尿和蛋白尿表现。该先证者通过与家族二相同的方法被诊断为IgAN。该女孩的祖父44岁时死于尿毒症。基因检测显示该女孩及其母亲携带COL4A5基因的杂合变异539G>A（Gly180Glu）。在家族一中鉴定出的CFHR5基因变异意义不确定，在家族二和三中鉴定出的COL4A5基因的两个变异是致病性的。家族二和三的先证者被诊断为Alport综合征。该研究表明，当先证者根据临床表现、肾脏病理和常规免疫组化被诊断为IgAN时，临床医生应检测血尿家族中FH相关基因的遗传变异。
