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Spectrum of mutations in Chinese children with steroid-resistant nephrotic syndrome

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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.

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Acknowledgements

We thank all patients and their families for participating in this study. This work was supported by National "Twelfth Five-Year" Science and Technology Support Project (No. 2012BAI03B02).

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    Authors and Affiliations

    1. Department of Pediatrics, Peking University First Hospital, No. 1, Xi An Men Da Jie, Beijing, 100034, People’s Republic of China

      Fang Wang, Yanqin Zhang, Fangrui Ding, Hongwen Zhang, Huijie Xiao, Yong Yao & Jie Ding

    2. Department of Nephrology, The Children Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China

      Jianhua Mao

    3. Department of Pediatrics, Fuzhou Dongfang Hospital, Fuzhou, People’s Republic of China

      Zihua Yu

    4. Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China

      Zhuwen Yi

    5. Department of Pediatrics, Guangzhou First People’s Hospital, Guangzhou, People’s Republic of China

      Li Yu

    6. Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-shenzhen, Tianjin, People’s Republic of China

      Jun Sun & Xiuxiu Wei

    7. BGI-Shenzhen, Shenzhen, People’s Republic of China

      Jun Sun & Xiuxiu Wei

    8. Division of Nephrology, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 561, Boston, MA, 02115, USA

      Weizhen Tan, Svjetlana Lovric & Friedhelm Hildebrandt

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    1. Fang Wang
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    Correspondence to Jie Ding or Friedhelm Hildebrandt.

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    The procedures were approved by the ethics committees of the five centers. After receiving informed consent from the patients or their family members, blood samples and comprehensive clinical data were collected and analyzed.

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    The authors declare that they have no conflicts of interest.

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    Jie Ding and Friedhelm Hildebrandt contributed equally to this work

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    Wang, F., Zhang, Y., Mao, J. et al. Spectrum of mutations in Chinese children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 32, 1181–1192 (2017). https://doi.org/10.1007/s00467-017-3590-y

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