Genetic Variations and Clinical Features of NPHS1-Related Nephrotic Syndrome in Chinese Children: A Multicenter, Retrospective Study

Liping Rong; Lizhi Chen; Jia Rao; Qian Shen; Guomin Li; Jialu Liu; Jianhua Mao; Chunyue Feng; Xiaowen Wang; Si Wang; Xinyu Kuang; Wenyan Huang; Qingshan Ma; Xiaorong Liu; Chen Ling; Rong Fu; Xiaojie Gao; Guixia Ding; Huandan Yang; Mei Han; Zhimin Huang; Qian Li; Qiuye Zhang; Yi Lin; Xiaoyun Jiang; Hong Xu

doi:10.3389/fmed.2021.771227

Genetic Variations and Clinical Features of NPHS1-Related Nephrotic Syndrome in Chinese Children: A Multicenter, Retrospective Study

Front Med (Lausanne). 2021 Nov 11:8:771227. doi: 10.3389/fmed.2021.771227. eCollection 2021.

Authors

Liping Rong¹, Lizhi Chen¹, Jia Rao², Qian Shen², Guomin Li², Jialu Liu², Jianhua Mao³, Chunyue Feng³, Xiaowen Wang⁴, Si Wang⁴, Xinyu Kuang⁵, Wenyan Huang⁵, Qingshan Ma⁶, Xiaorong Liu⁷, Chen Ling⁷, Rong Fu⁸, Xiaojie Gao⁹, Guixia Ding¹⁰, Huandan Yang¹¹, Mei Han¹², Zhimin Huang¹³, Qian Li¹⁴, Qiuye Zhang¹⁵, Yi Lin¹⁵, Xiaoyun Jiang¹, Hong Xu²

Affiliations

¹ Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
² Department of Nephrology, Children's Hospital of Fudan University, Shanghai, China.
³ Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁴ Department of Nephrology and Rheumatology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
⁵ Department of Nephrology and Rheumatology, Children's Hospital of Shanghai Jiaotong University, Shanghai, China.
⁶ Department of Pediatric Nephrology, First Hospital, Jilin University, Changchun, China.
⁷ Department of Nephrology, Bejing Children's Hospital Affiliated to Capital University of Medical Science, Beijing, China.
⁸ Department of Pediatrics, Puyang Oilfield General Hospital, Puyang, China.
⁹ Department of Nephrology, Shenzhen Children's Hospital, Shenzhen, China.
¹⁰ Department of Nephrology, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, China.
¹¹ Department of Nephrology, Xuzhou Children's Hospital, Xuzhou, China.
¹² Department of Nephrology, Children's Hospital of Dalian Medical University, Dalian, China.
¹³ Department of Pediatrics, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
¹⁴ Department of Pediatric Nephrology, Rheumatism and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong, China.
¹⁵ Department of Pediatrics, Affiliated Hospital of Qingdao University, Qingdao, China.

Abstract

Introduction: Few studies have addressed the genetic spectrum of NPHS1 variants in Chinese children with nephrotic syndrome. In this multicenter study, the clinical manifestations and features of NPHS1 variants in Chinese children with nephrotic syndrome were researched. Method: Genotypical and phenotypical data from 30 children affected by NPHS1 variants were collected from a multicenter registration system in China and analyzed retrospectively. Results: The patients were divided into two groups: congenital nephrotic syndrome (CNS [n = 24]) and non-CNS (early onset nephrotic syndrome [n = 6]). Renal biopsy was performed on four patients in the non-CNS group, revealing minimal change disease in three and focal segmental glomerulosclerosis in one. A total of 61 NPHS1 variants were detected, involving 25 novel variants. The "recurrent variants" included c.928G>A(p.Asp310Asn) in eight patients with CNS, followed by c.616C>A(p.Pro206Thr) in four, and c.2207T>C (p.Val736Ala) in three. Steroid treatment was applied in 29.2% (7/24)of the patients in the CNS group and 50% (3/6) of the patients in the non-CNS group. One patient in each group experienced complete remission but relapsed subsequently. Immunosuppressants were administered to three patients in the non-CNS group, eliciting an effective response. In the CNS group, three patients underwent renal transplantation and six died mainly from infection. Conclusion: Variants of NPHS1 cause CNS and early childhood-onset nephrotic syndrome. NPHS1 variants in Chinese individuals with nephrotic syndrome (NS) were mainly compound heterozygous variants, and c.928G>A(p.Asp310Asn) in exon 8 may act as a recurrent variant in the Chinese population, followed by c.616C>A(p.Pro206Thr) in exon 6. Steroids and immunosuppressants may be effective in selected patients.

Keywords: NPHS1; children; congenital nephrotic syndrome; multicenter; steroid resistance; variants.