title: Spectrum of mutations in Chinese children with steroid-resistant nephrotic syndrome.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1, Xi An Men Da Jie, Beijing, 100034, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1, Xi An Men Da Jie, Beijing, 100034, People's Republic of China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, The Children Hospital of Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Pediatrics, Fuzhou Dongfang Hospital, Fuzhou, People's Republic of China.
authors.forename: Zihua
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.
authors.forename: Zhuwen
authors.initials: Z
authors.lastname: Yi
authors.affiliation: Department of Pediatrics, Guangzhou First People's Hospital, Guangzhou, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-shenzhen, Tianjin, People's Republic of China.|BGI-Shenzhen, Shenzhen, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.affiliation: Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-shenzhen, Tianjin, People's Republic of China.|BGI-Shenzhen, Shenzhen, People's Republic of China.
authors.forename: Xiuxiu
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1, Xi An Men Da Jie, Beijing, 100034, People's Republic of China.
authors.forename: Fangrui
authors.initials: F
authors.lastname: Ding
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1, Xi An Men Da Jie, Beijing, 100034, People's Republic of China.
authors.forename: Hongwen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1, Xi An Men Da Jie, Beijing, 100034, People's Republic of China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1, Xi An Men Da Jie, Beijing, 100034, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Division of Nephrology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 561, Boston, MA, 02115, USA.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Tan
authors.affiliation: Division of Nephrology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 561, Boston, MA, 02115, USA.
authors.forename: Svjetlana
authors.initials: S
authors.lastname: Lovric
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1, Xi An Men Da Jie, Beijing, 100034, People's Republic of China. djnc_5855@126.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: Division of Nephrology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 561, Boston, MA, 02115, USA. friedhelm.hildebrandt@childrens.harvard.edu.
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D020125:Mutation, Missense; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000188:drug therapy / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics; D011507:Proteinuria / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D000074287:TRPC6 Cation Channel / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics
chemical_list: D005938:Glucocorticoids; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D025721:WT1 Proteins; C583751:WT1 protein, human; C113267:nephrin; C586096:COQ8B protein, human; D011494:Protein Kinases
keywords: Children; Chinese; Gene; Steroid-resistant nephrotic syndrome