A Systematic Analysis of Major Susceptible Genes in Childhood-onset Steroid-resistant Nephrotic Syndrome

Abstract

Aim: Nephrotic syndrome is a urinary disease, causing high morbidity and mortality. However, the mutation prevalence of major susceptible genes in childhood-onset steroid-resistant nephrotic syndrome (SRNS) in China is limited. In this study, we performed a systematic analysis of the mutations in 18 major SRNS-susceptible genes in Chinese SRNS children.

Methods: Mutation analysis was performed to sequence 18 major SRNS-susceptible genes (NPHS1, NPHS2, CD2AP, PLCE1, ACTN4, TRPC6, INF2, WT1, LMX1B, LAMB2, LAMB3, GLA, ITGB4, SCARB2, COQ2, PDSS2, MTTL1, and SMARCAL1) using a PCR-based MassArray technology in 38 childhood-onset SRNS patients in China. This cohort included 10 sporadic cases and 28 familial cases from 7 SRNS families with disease onset between the ages of 1-13 years.

Results: Our analysis detected a heterozygous missense mutation (p.E447K, pathogenic) in NPHS1 in 3/28 familial patients (10.7%) and 1/10 (10.0%) patient without a family history. In addition, two NPHS2 mutations (p.R138X and p.R291W, pathogenic) were identified in 2 patients from another family (7.1% familial cases, 0% sporadic cases, 5.2% overall). Pathogenic mutations of remaining 16 SRNS-susceptible genes were not detected.

Conclusion: Our results have verified the significant prevalence of pathogenic NPHS1 and NPHS2 mutations in childhood-onset SRNS in China, while the other 16 SRNS-susceptible genes seem to have lesser contribution to child-onset SRNS. Therefore, our study indicates that it is very necessary to make more efforts to target NPHS1 and NPHS2 for childhood-onset SRNS treatment, especially in China.

Keywords: NPHS1; NPHS2; childhood-onset; gene mutation; steroid-resistant nephrotic syndrome.