Association Of ACTN4 Gene Mutation With Primary Nephrotic Syndrome In Zhuang Children In Guangxi

Objective: To investigate the association between ACTN4 gene mutation and primary nephrotic syndrome in Zhuang children in Guangxi.Methods:(1)A second-generation sequencing technology was used to sequence ACTN4 gene in 155 children with primary nephrotic syndrome in Guangxi Zhuang nationality(focal segmental glomerulosclerosis in 47 cases,minimal change nephrosis in 45 cases,IgA nephropathy in 36 cases,membranous nephropathy in 9 cases,no renal puncture in 18 cases).23 exon-specific capture probes of ACTN4 were designed and hybridized with the genomic DNA library.The target genomic region DNA fragments were enriched,and then sequenced by Illumina Nextseq second-generation sequencer,and compared with 98 healthy children in Guangxi Zhuang nationality and related bioinformatics analysis to determine the mutation sites.(2)Elisa method was used to detect ACTN4 protein content in case group and control group,and comparative analysis was performed.Results:(1)After data analysis and bioinformatics analysis,5 heterozygous mutations of ACTN4 gene in the case group were found,including 2 cases of c.1516G>A(p.G506S)and 1case of c.1442+10G>A.c.1649A> G(p.D550G)1 case,c.2191-4G> A 2 case,and c.2315C> T(p.A772V)1 case,including c.1649A> G(p.D550G)and c.2315C> T(p.A772V)was detected in the same child,but due to the limited number of studies,it was unable to prove whether the two mutations were linked,and c.1649A>G(p.D550G)was a newly discovered heterozygous mutation;(2)Three ACTN4 potential heterozygous mutations occurred in both case group and healthy group,including c.162+6C>T(1 case in the diseasegroup and 2 cases in the healthy group),c.572+11G>A(1 case in the disease group,2 cases in the healthy group)and c.2191-5C>T(4 cases in the diseased group and 3 cases in the healthy group);(2)ACTN4 serum level of healthy group was 544.7(264.6,952.6)ng / mL,which was significantly higher than that of nephrotic syndrome group 241.20(110.75,542.35)ng / mL.Conclusion:(1)At home and abroad,ACTN4 gene mutations have been reported as autosomal dominant familial focal segmental glomerulosclerosis.This study also found ACTN4 gene Disease mutation in other pathological types of primary nephrotic syndrome in Zhuang children in Guangxi;(2)The three ACTN4 heterozygous mutations were detected in both the case group and the healthy group.The ACTN4 heterozygous mutation detected in the healthy control group was considered to be a potential pathogenic mutation and has not yet occurred;(3)The serum ACTN4 protein level in the healthy group was significantly higher than that in the nephrotic syndrome group.The serum ACTN4 protein level may be a protective protein for the primary nephritic syndrome in Zhuang children in Guangxi.