Wang Fang, Zhang Yanqin, Mao Jianhua, Yu Zihua, Yi Zhuwen, Yu Li, Sun Jun, Wei Xiuxiu, Ding Fangrui, Zhang Hongwen, Xiao Huijie, Yao Yong, Tan Weizhen, Lovric Svjetlana, Ding Jie, Hildebrandt Friedhelm
Department of Pediatrics, Peking University First Hospital, No. 1, Xi An Men Da Jie, Beijing, 100034, People's Republic of China.
Department of Nephrology, The Children Hospital of Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Pediatr Nephrol. 2017 Jul;32(7):1181-1192. doi: 10.1007/s00467-017-3590-y. Epub 2017 Feb 15.
The aim of this study was to elucidate whether genetic screening test results of pediatric patients with steroid-resistant nephrotic syndrome (SRNS) vary with ethnicity.
Using high-throughput DNA sequencing, 28 nephrotic syndrome-related genes were analyzed in 110 chil-dren affected by SRNS and 10 children with isolated proteinuria enrolled by 5 centers in China (67 boys, 53 girls). Their age at disease onset ranged from 1 day to 208 months (median, 48.8 months). Patients were excluded if their age at onset of disease was over 18 years or if they were diagnosed as having Alport syndrome.
A genetic etiology was identified in 28.3% of our cohort and the likelihood of establishing a genetic diagnosis decreased as the age at onset of nephrotic syndrome increased. The most common mutated genes were ADCK4 (6.67%), NPHS1 (5.83%), WT1 (5.83%), and NPHS2 (3.33%), and the difference in the frequencies of ADCK4 and NPHS2 mutations between this study and a study on monogenic causes of SRNS in the largest international cohort of 1,783 different families was significant. A case of congenital nephrotic syndrome was attributed to a homozygous missense mutation in ADCK4, and a de novo missense mutation in TRPC6 was detected in a case of infantile nephrotic syndrome.
Our results showed that, in the first and the largest multicenter cohort of Chinese pediatric SRNS reported to date, ADCK4 is the most common causative gene, whereas there is a low prevalence of NPHS2 mutations. Our data indicated that the genetic testing results for pediatric SRNS patients vary with different ethnicities, and this information will help to improve management of the disease in clinical practice.
本研究旨在阐明激素抵抗型肾病综合征（SRNS）患儿的基因筛查检测结果是否因种族而异。
采用高通量DNA测序技术，对中国5个中心招募的110例SRNS患儿和10例孤立性蛋白尿患儿（67例男孩，53例女孩）的28个肾病综合征相关基因进行分析。他们发病时的年龄从1天到208个月不等（中位数为48.8个月）。如果发病年龄超过18岁或被诊断为Alport综合征，则将患者排除。
在我们的队列中，28.3%的患者确定了遗传病因，肾病综合征发病年龄越大，建立遗传诊断的可能性越低。最常见的突变基因是ADCK4（6.67%）、NPHS1（5.83%）、WT1（5.83%）和NPHS2（3.33%），本研究与最大的国际队列中1783个不同家庭的SRNS单基因病因研究中ADCK4和NPHS2突变频率的差异具有统计学意义。1例先天性肾病综合征归因于ADCK4的纯合错义突变，1例婴儿型肾病综合征检测到TRPC6的新发错义突变。
我们的结果表明，在迄今为止报道的首个也是最大的中国儿童SRNS多中心队列中，ADCK4是最常见的致病基因，而NPHS2突变的患病率较低。我们的数据表明，SRNS患儿的基因检测结果因种族而异，这些信息将有助于改善临床实践中该疾病的管理。
