中国儿童肾脏和泌尿系统疾病的遗传结构
Genetic Architecture of Childhood Kidney and Urological Diseases in China.
作者信息
Fang Ye, Shi Hua, Xiang Tianchao, Liu Jiaojiao, Liu Jialu, Tang Xiaoshan, Fang Xiaoyan, Chen Jing, Zhai Yihui, Shen Qian, Li Guomin, Sun Li, Bi Yunli, Wang Xiang, Qian Yanyan, Wu Bingbing, Wang Huijun, Zhou Wenhao, Ma Duan, Mao Jianhua, Jiang Xiaoyun, Sun Shuzhen, Shen Ying, Liu Xiaorong, Zhang Aihua, Wang Xiaowen, Huang Wenyan, Li Qiu, Wang Mo, Gao Xiaojie, Wu Yubin, Deng Fang, Zhang Ruifeng, Liu Cuihua, Yu Li, Zhuang Jieqiu, Sun Qing, Dang Xiqiang, Bai Haitao, Zhu Ying, Lu Siguang, Zhang Bili, Shao Xiaoshan, Liu Xuemei, Han Mei, Zhao Lijun, Liu Yuling, Gao Jian, Bao Ying, Zhang Dongfeng, Ma Qingshan, Zhao Liping, Xia Zhengkun, Lu Biao, Wang Yulong, Zhao Mengzhun, Zhang Jianjiang, Jian Shan, He Guohua, Zhang Huifeng, Zhao Bo, Li Xiaohua, Wang Feiyan, Li Yufeng, Zhu Hongtao, Luo Xinhui, Li Jinghai, Rao Jia, Xu Hong
机构信息
Department of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of CHINA, 399 Wanyuan Road, Shanghai, China.
Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
出版信息
Phenomics. 2021 Jul 15;1(3):91-104. doi: 10.1007/s43657-021-00014-1. eCollection 2021 Jun.
UNLABELLED
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 implemented 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.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s43657-021-00014-1.
未标注
肾病表现为多种表型，其中许多具有重要的遗传成分。为了描绘儿童肾病的基因型和表型谱，正在基于中国儿童遗传性肾病数据库（CCGKDD）实施一个多中心登记系统。在本研究中，2014年至2020年招募了所有患有肾脏和泌尿系统疾病的患者。对有多例肾病患者或因早发或肾外特征而临床怀疑患有遗传性肾病的家庭，使用外显子组测序进行基因分析。在中国23个省份的2256例患者中，有883例（39.1%）确诊了基因诊断。表型特征显示，主要诊断包括激素抵抗性肾病综合征（SRNS，23.5%）、肾小球肾炎（GN，32.2%）、肾脏和尿路先天性异常（CAKUT，21.2%）、囊性肾病（3.9%）、肾钙质沉着症/结石（3.6%）、肾小管病（9.7%）以及病因不明的慢性肾病（CKDu，5.8%）。鉴定出了105种单基因疾病的致病变异。在11例患者中鉴定出10种不同的基因组疾病为致病性拷贝数变异（CNV）。诊断率因亚组而异，在囊性肾病患者中最高（66.3%），其次是肾小管病（58.4%）、GN（57.7%）、CKDu（43.5%）、SRNS（29.2%）、肾钙质沉着症/结石（29.3%）和CAKUT（8.6%）。反向表型分析在40例经临床重新评估和意外基因状况的病例中实现了正确识别。我们展示了中国最大的进行诊断性外显子组测序的肾病儿童队列的结果。我们的数据证明了基于家系的外显子组测序的实用性，并表明基于全国患者登记系统的基因型和表型联合分析对于肾病的基因诊断至关重要。
补充信息
在线版本包含可在10.1007/s43657-021-00014-1获取的补充材料。
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