Genetic Architecture of Childhood Kidney and Urological Diseases in China  

作　　者：Ye Fang Hua Shi Tianchao Xiang Jiaojiao Liu Jialu Liu Xiaoshan Tang Xiaoyan Fang Jing Chen Yihui Zhai Qian Shen Guomin Li Li Sun Yunli Bi Xiang Wang Yanyan Qian Bingbing Wu Huijun Wang Wenhao Zhou Duan Ma Jianhua Mao Xiaoyun Jiang Shuzhen Sun Ying Shen Xiaorong Liu Aihua Zhang Xiaowen Wang Wenyan Huang Qiu Li Mo Wang Xiaojie Gao Yubin Wu Fang Deng Ruifeng Zhang Cuihua Liu Li Yu Jieqiu Zhuang Qing Sun Xiqiang Dang Haitao Bai Ying Zhu Siguang Lu Bili Zhang Xiaoshan Shao Xuemei Liu Mei Han Lijun Zhao Yuling Liu Jian Gao Ying Bao Dongfeng Zhang Qingshan Ma Liping Zhao Zhengkun Xia Biao Lu Yulong Wang Mengzhun Zhao Jianjiang Zhang Shan Jian Guohua He Huifeng Zhang Bo Zhao Xiaohua LI Feiyan Wang Yufeng Li Hongtao Zhu Xinhui Luo Jinghai Li Jia Rao Hong Xu 

机构地区：[1]Department of Nephrology,Children’s Hospital of Fudan University,National Pediatric Medical Center of CHINA,399 Wanyuan Road,Shanghai,China [2]Shanghai Kidney Development and Pediatric Kidney Disease Research Center,Shanghai,China [3]Shanghai Key Lab of Birth Defect,Children’s Hospital of Fudan University,Shanghai 201102,China [4]Department of Rheumatology,Children’s Hospital of Fudan University,Shanghai,China [5]Department of Urology,Children’s Hospital of Fudan University,Shanghai,China [6]Clinical Genetic Center,Children’s Hospital of Fudan University,Shanghai,China [7]Key Laboratory of Metabolism and Molecular Medicine,Ministry of Education,Department of Biochemistry and Molecular Biology,Institutes of Biomedical Sciences,School of Basic Medical Sciences,Fudan University,Shanghai,China [8]The Children Hospital of Zhejiang University School of Medicine,Hangzhou,China [9]The First Affiliated Hospital of Sun Yat-Sen University,Guangzhou,China [10]Shandong Provincial Hospital,Jinan,China [11]Bejing Children’s Hospital Affiliated to Capital University of Medical Science,Beijing,China [12]Children’s Hospital of Nanjing Medical University,Nanjing,China [13]Wuhan Children’s Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [14]Shanghai Children’s Medical Centre,Shanghai Jiaotong University School of Medicine,Shanghai,China [15]Children’s Hospital of Chongqing Medical University,Chongqing,China [16]Shenzhen Children’s Hospital,Shenzheng,China [17]Shengjing Hospital of China Medical University,Shenyang,Liaoning,China [18]Anhui Provincial Children’s Hospital,Hefei,China [19]Xuzhou Children’s Hospital,Xuzhou,China [20]Henan Children’s Hospital,Zhengzhou,China [21]Guangzhou First People’s Hospital,Guangzhou,China [22]The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,China [23]Qingdao Women and Children’s Hospital,Qingdao,China [24]Xiangya Hospital Central South University,Changsha,Hunan,China [25]

出　　处：《Phenomics》2021年第3期91-104,共14页表型组学（英文）

基　　金：J.R.is supported by National Natural Science Foundation of China(NSFC-8182207);Shanghai Academic/Technology Research Leader(19XD1420600);Chinese Academy of Medical Sciences(2019-RC-HL_020).

摘　　要：Kidney disease is manifested in a wide variety of phenotypes,many of which have an important hereditary component.To delineate the genotypic and phenotypic spectrum of pediatric nephropathy,a multicenter registration system is being imple-mented based on the Chinese Children Genetic Kidney Disease Database(CCGKDD).In this study,all the patients with kidney and urological diseases were recruited from 2014 to 2020.Genetic analysis was conducted using exome sequencing for families with multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early-onset or extrarenal features.The genetic diagnosis was confirmed in 883 of 2256(39.1%)patients from 23 provinces in China.Phenotypic profiles showed that the primary diagnosis included steroid-resistant nephrotic syndrome(SRNS,23.5%),glomerulonephritis(GN,32.2%),congenital anomalies of the kidney and urinary tract(CAKUT,21.2%),cystic renal disease(3.9%),renal calcinosis/stone(3.6%),tubulopathy(9.7%),and chronic kidney disease of unknown etiology(CKDu,5.8%).The pathogenic variants of 105 monogenetic disorders were identified.Ten distinct genomic disorders were identified as pathogenic copy number variants(CNVs)in 11 patients.The diagnostic yield differed by subgroups,and was highest in those with cystic renal disease(66.3%),followed by tubulopathy(58.4%),GN(57.7%),CKDu(43.5%),SRNS(29.2%),renal calcinosis/stone(29.3%)and CAKUT(8.6%).Reverse phenotyping permitted correct identification in 40 cases with clinical reassessment and unexpected genetic conditions.We present the results of the largest cohort of children with kidney disease in China where diagnostic exome sequencing was performed.Our data demonstrate the utility of family-based exome sequencing,and indicate that the combined analysis of genotype and phenotype based on the national patient registry is pivotal to the genetic diagnosis of kidney disease.

关 键 词：Chronic kidney disease(CKD) Exome sequencing(ES) Steroid-resistant nephrotic syndrome(SRNS) Congenital anomalies of the kidney and urinary tract(CAKUT) Nephronophthisis(NPHP) Polycystic kidney disease(PKD) 

分 类 号：R69[医药卫生—泌尿科学]