Mutational spectrum and novel candidate genes in Chinese children with sporadic steroid-resistant nephrotic syndrome



Approximately 10–20% of children with idiopathic nephrotic syndrome (NS) fail to respond to steroid therapy. NS is divided into steroid-sensitive NS (SSNS) and steroid-resistant NS (SRNS). Over 45 recessive and dominant genes have been found to be associated with SRNS and/or focal segmental glomerulosclerosis (FSGS).


Targeted sequencing of 339 candidate genes, expressed in glomerular filtration barrier or located in the signaling pathway of podocyte function, were sequenced by NGS in a cohort of total 89 Chinese Han children (29 sporadic SRNS, 33 sporadic SSNS, and 27 healthy).


Two variants (WT1 p.R441X and NPHS2 p.G149V) were screened out as pathogenic mutations and 14 variants were likely pathogenic. Mutations of KIRREL2 (SRNS vs SSNS: 24.1% vs 3.0%, adjusted OR = 10.11, 95% CI: 1.56–198.66, P = 0.039) were significantly associated with the risk of pediatric sporadic SRNS. Besides, three pathogenic or likely pathogenic variants were identified in HP gene.


Two pathogenic mutations and 14 likely pathogenic mutations were discovered through targeted sequencing of 339 candidate genes. Two genes, HP and KIRREL2, as candidate genes, were first proposed to be associated with the risk of pediatric sporadic SRNS.

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We are indebted to the patients and families for participating in this study and to the clinical teams involved in recruitment and sample collection. This work was supported by the National Natural Science Foundation of China (81100504, 81570649).

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Correspondence to Jianguo Li.

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