Genetic spectrum of renal disease for 1001 Chinese children based on a multicenter registration system

Jia Rao^{1

2

3}, Xiaorong Liu^{4

5}, Jianhua Mao⁶, Xiaoshan Tang^{1

2

7}, Qian Shen^{1

2

7}, Guomin Li^{2

8}, Li Sun^{2

8}, Yunli Bi^{2

9}, Xiang Wang^{2

9}, Yanyan Qian¹⁰, Bingbing Wu¹⁰, Huijun Wang¹⁰, Wenhao Zhou¹⁰, Duan Ma¹¹, Bixia Zheng¹², Ying Shen^{4

5}, Zhi Chen^{4

5}, Jiangwei Luan¹³, Xiaowen Wang¹³, Mo Wang¹⁴, Xiqiang Dang¹⁵, Ying Wang¹⁵, Yubing Wu¹⁶, Ling Hou¹⁶, Shuzhen Sun¹⁷, Qian Li¹⁷, Xuemei Liu¹⁸, Haitao Bai¹⁹, Yang Yang¹⁹, Xiaoshan Shao²⁰, Yuhong Li²⁰, Shasha Zheng²⁰, Mei Han²¹, Cuihua Liu²², Guanghai Cao²², Lijun Zhao²³, Sanling Qiu²³, Yang Dong²⁴, Ying Zhu²⁴, Feiyan Wang²⁵, Dongfeng Zhang²⁶, Yufeng Li²⁷, Liping Zhao²⁸, Chunfang Yang²⁹, Xinhui Luo³⁰, Lizhi Chen³¹, Xiaoyun Jiang³¹, Aihua Zhang³², Hong Xu^{1

2

7}; for “Internet Plus” Nephrology Alliance of National Center for Children's Care

Affiliations

¹ Department of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China.
² Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
³ State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and School of Basic Medical Science, Fudan University.
⁴ Department of Nephrology, Beijing Children's Hospital Affiliated to Capital University of Medical Science, Beijing, China.
⁵ Beijing Children's Key Laboratory of Chronic Kidney Disease and Blood Purification, Beijing, China.
⁶ Department of Nephrology, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁷ Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China.
⁸ Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
⁹ Department of Urology, Children's Hospital of Fudan University, Shanghai, China.
¹⁰ Clinical Genetic Center, Children's Hospital of Fudan University, Shanghai, China.
¹¹ Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
¹² Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
¹³ Department of Nephrology and Rheumatology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁴ Department of Nephrology and Rheumatology, Children's Hospital of Chongqing Medical University, Chongqing, China.
¹⁵ Department of Pediatric, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
¹⁶ Department of Pediatric Renal Rheumatism Immunology, Shengjing Hospital Affiliated to China Medical University, Shenyang, China.
¹⁷ Department of Pediatric Nephrology, Rheumatism and Immunology, Shandong Provincial Hospital, Shandong University.
¹⁸ Department of Nephrology, Rheumatology and Immunology, Qilu Children's Hospital of Shandong University, Jinan, China.
¹⁹ Department of Pediatric, The First Affiliated Hospital of Xiamen University, Xiamen, China.
²⁰ Department of Nephrology, The Children's Hospital of Guiyang City, Guiyang, China.
²¹ Department of Nephrology, Children's Hospital of Dalian Medical University, Dalian, China.
²² Department of Nephrology and Rheumatology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
²³ Department of Nephrology, Shanxi Provincial Children's Hospital, Taiyuan, China.
²⁴ Department of Nephrology, Anhui Provincial Children's Hospital, Hefei, China.
²⁵ Department of Pediatric, Urumqi City Children's Hospital, Urumqi, China.
²⁶ Department of Nephrology and Immunology, Children's Hospital of Hebei Province, Shijiazhuang, China.
²⁷ Department of Pediatric Nephrology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
²⁸ Department of Nephrology, Wuxi Children's Hospital, Wuxi, China.
²⁹ Department of Pediatric, the First Affiliated Hospital of the University of Science and Technology of China (USTC), Hefei, China.
³⁰ Department of Pediatric, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi, China.
³¹ Department of Pediatric, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
³² Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.

PMID: 31328266
DOI: 10.1111/cge.13606

Multicenter Study

Genetic spectrum of renal disease for 1001 Chinese children based on a multicenter registration system

Jia Rao et al. Clin Genet. 2019 Nov.

. 2019 Nov;96(5):402-410.

doi: 10.1111/cge.13606. Epub 2019 Jul 25.

Authors

Affiliations

¹ Department of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China.
² Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
³ State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and School of Basic Medical Science, Fudan University.
⁴ Department of Nephrology, Beijing Children's Hospital Affiliated to Capital University of Medical Science, Beijing, China.
⁵ Beijing Children's Key Laboratory of Chronic Kidney Disease and Blood Purification, Beijing, China.
⁶ Department of Nephrology, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁷ Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China.
⁸ Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
⁹ Department of Urology, Children's Hospital of Fudan University, Shanghai, China.
¹⁰ Clinical Genetic Center, Children's Hospital of Fudan University, Shanghai, China.
¹¹ Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
¹² Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
¹³ Department of Nephrology and Rheumatology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁴ Department of Nephrology and Rheumatology, Children's Hospital of Chongqing Medical University, Chongqing, China.
¹⁵ Department of Pediatric, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
¹⁶ Department of Pediatric Renal Rheumatism Immunology, Shengjing Hospital Affiliated to China Medical University, Shenyang, China.
¹⁷ Department of Pediatric Nephrology, Rheumatism and Immunology, Shandong Provincial Hospital, Shandong University.
¹⁸ Department of Nephrology, Rheumatology and Immunology, Qilu Children's Hospital of Shandong University, Jinan, China.
¹⁹ Department of Pediatric, The First Affiliated Hospital of Xiamen University, Xiamen, China.
²⁰ Department of Nephrology, The Children's Hospital of Guiyang City, Guiyang, China.
²¹ Department of Nephrology, Children's Hospital of Dalian Medical University, Dalian, China.
²² Department of Nephrology and Rheumatology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
²³ Department of Nephrology, Shanxi Provincial Children's Hospital, Taiyuan, China.
²⁴ Department of Nephrology, Anhui Provincial Children's Hospital, Hefei, China.
²⁵ Department of Pediatric, Urumqi City Children's Hospital, Urumqi, China.
²⁶ Department of Nephrology and Immunology, Children's Hospital of Hebei Province, Shijiazhuang, China.
²⁷ Department of Pediatric Nephrology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
²⁸ Department of Nephrology, Wuxi Children's Hospital, Wuxi, China.
²⁹ Department of Pediatric, the First Affiliated Hospital of the University of Science and Technology of China (USTC), Hefei, China.
³⁰ Department of Pediatric, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi, China.
³¹ Department of Pediatric, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
³² Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.

PMID: 31328266
DOI: 10.1111/cge.13606

Abstract

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.

Keywords: chronic kidney disease (CKD); congenital anomalies of the kidney and urinary tract (CAKUT); genetics; nephronophthisis (NPHP); polycystic kidney disease PKD; renal disease; singleton-WES; steroid-resistant nephrotic syndrome (SRNS); targeted gene sequence (TGS); trio approach for WES (trio-WES); whole-exome sequence (WES).

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Comment in

Genetic architecture of paediatric renal diseases in China and the need for data sharing.
Bierzynska A, Saleem MA. Bierzynska A, et al. Transl Pediatr. 2020 Jun;9(3):202-205. doi: 10.21037/tp-20-135. Transl Pediatr. 2020. PMID: 32775236 Free PMC article. No abstract available.

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Genetic spectrum of renal disease for 1001 Chinese children based on a multicenter registration system

Affiliations

Genetic spectrum of renal disease for 1001 Chinese children based on a multicenter registration system

Authors

Affiliations

Abstract

Comment in

References

REFERENCES

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical