1. Spectrum of mutations in Chinese children with steroid-resistant nephrotic syndrome
- Author
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Huijie Xiao, Jun Sun, Fangrui Ding, Yong Yao, Zihua Yu, Friedhelm Hildebrandt, Hongwen Zhang, Xiuxiu Wei, Jie Ding, Zhuwen Yi, Jianhua Mao, Yanqin Zhang, Svjetlana Lovric, Fang Wang, Li Yu, and Weizhen Tan
- Subjects
Male ,0301 basic medicine ,Nephrology ,China ,Pediatrics ,medicine.medical_specialty ,Nephrotic Syndrome ,Adolescent ,DNA Mutational Analysis ,Drug Resistance ,Mutation, Missense ,030232 urology & nephrology ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Internal medicine ,TRPC6 Cation Channel ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Age of Onset ,Child ,WT1 Proteins ,Glucocorticoids ,business.industry ,Homozygote ,Infant, Newborn ,Intracellular Signaling Peptides and Proteins ,High-Throughput Nucleotide Sequencing ,Infant ,Membrane Proteins ,Sequence Analysis, DNA ,medicine.disease ,Steroid-resistant nephrotic syndrome ,Genetic screening test ,Proteinuria ,030104 developmental biology ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,business ,Protein Kinases ,Nephrotic syndrome - Abstract
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.
- Published
- 2017