Yongzhen Li1,2, Qingnan He3,2, Ying Wang1,2, Xiqiang Dang1,2, Xiaochuan Wu1,2, Xiaoyan Li1,2, Lanjun Shuai1,2, Zhuwen Yi3,2. 1. Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. 2. Laboratory of Pediatric Nephrology, Institute of Pediatrics, Central South University, Changsha, Hunan, China. 3. Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China heqn2629@csu.edu.cn.
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.
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.