Department of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China.
Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
Clin Genet. 2019 Nov;96(5):402-410. doi: 10.1111/cge.13606. Epub 2019 Jul 25.
To explore the approaches and diagnostic yield of genetic testing for renal disease in children, we describe the genotype and phenotype of the national cohort of children with renal disease from 13 different regions of China recruited from 2014 to 2018 by building up the multicenter registration system (Chinese Children Genetic Kidney Disease Database, CCGKDD). Genetic diagnosis was confirmed in 42.1% of our cohort of 1001 pediatric patients with clinical suspicion of a genetic renal disease. Of the 106 distinct monogenetic disorders detected, 15 accounted for 60.7% of genetic diagnoses. The diagnostic yield was 29.1% in steroid resistant nephritic syndrome (SRNS), 61.4% in cystic renal disease, 17.0% in congenital anomalies of the kidney and urinary tract (CAKUT), 62.3% in renal tubular disease/renal calcinosis, and 23.9% for chronic kidney disease (CKD) 3 to 5 stage with unknown origin. Genetic approaches of target gene sequence (TGS), singleton whole-exome sequencing (WES) and trio-WES were performed with diagnostic rates of 44.8%, 36.2%, and 42.6%, respectively. The early use of trio-WES could improve the diagnostic rate especially in renal tubular disease and calcinosis. We report the genetic spectrum of Chinese children with renal disease. Establishment of the CCGKDD will improve the genetic work on renal disease.
为了探索儿童肾脏疾病基因检测的方法和诊断率，我们描述了中国 13 个不同地区的 1001 名有临床疑似遗传性肾脏疾病的患儿的基因型和表型，这些患儿是通过建立多中心登记系统（中国儿童遗传性肾脏疾病数据库，CCGKDD）于 2014 年至 2018 年招募的。在我们的 1001 名儿科患者队列中，有 42.1%的患者被确诊为遗传性疾病。在检测到的 106 种不同的单基因疾病中，15 种疾病占遗传诊断的 60.7%。在类固醇抵抗性肾病综合征（SRNS）中，诊断率为 29.1%，囊性肾病为 61.4%，先天性肾和尿路异常（CAKUT）为 17.0%，肾小管疾病/肾钙化症为 62.3%，慢性肾脏病（CKD）3 至 5 期病因不明为 23.9%。目标基因序列（TGS）、单体全外显子测序（WES）和 trio-WES 的基因检测方法的诊断率分别为 44.8%、36.2%和 42.6%。早期使用 trio-WES 可以提高诊断率，特别是在肾小管疾病和钙化症方面。我们报告了中国儿童肾脏疾病的遗传谱。CCGKDD 的建立将提高肾脏疾病的遗传研究水平。
