Correlation Between PLCE1 Gene Mutation And Children With Primary Nephrotic Syndrome In Zhuang,Guangxi,China

Objective: To Analysis the mutation sites and characteristics of PLCE1 Gene in Zhuang children with Primary Nephrotic Syndrome in in Zhuang,Guangxi,China,explore the expression characteristics of PLCE1 protein in peripheral blood of PNS patients.Methods:(1)Blood samples of 155 Zhuang children with PNS and 98 healthy children of the Zhuang nationality were collected to sequence 34 exon of PLCE1 gene by next generation sequencing.Based on the comparison between mutation results and imformation from the database,the pathogenicity,phenotype and distribution characteristics of these mutation sites were found and appraised.(2)The concentration of PLCE1 protein in the serum samples were measured by ELISA,then the data of case group and normal groups were compared and analyzed statistically by SPSS 25.0.Results:(1)A total of 9 low-frequency mutations of PLCE1 in the case group were found,six of them were found only in the case group:c.670C>T: p.P224S、c.923G>T:p.G308A、c.4916C>T:p.A1639V、c.5927＿5929del:p.1976＿1977del、c.6885+12C>G in one case each,c.578T>C:p.V193 A in 2 cases.Three mutations occurred in both case and control groups:c.176C>T:p.T59M(1 case in case group,1case in control group)、 c.389T>C :p.V130A(2 cases in case group,1case in control group)、c.4304C>T:p.T1435M(2 cases in case group,1case in control group).Six newly discovered mutations were found by comparing databases: c.923G>T:p.G308 A 、 c.958T>A:p.L320 M 、 c.1151C>T:p.T384 I 、c.2341A>G:p.K781E、c.3592G>C:p.G1198R、c.6885+12C>G in one case each.(2)Amongthe 155 patients with PNS,137 patients received renal biopsy and 18 patients refused.Focal Segmental glomerular Sclerosis(FSGS)account for 34.3% of the total pathological findings,Minimal Change Nephrosis(MCN)account for 32.85% of the total,Ig A Nephropathyaccount for 26.28% of the total,Membranous Nephropathy(MN)account for 6.57% of the total.12cases(9 mutations)of low-frequency mutations were detected in the children with PLCE1 mutations,all of which were heterozygous mutations.Except for 1 case that had not received renal pathological examination,8 cases of MCN,2 cases of MN,and 1 case of Ig A nephropathy were detected in the other 11 children.Fifteen children with low frequency mutation of PLCE1 were found in the control group.(3)The concentration of PLCE1 protein in the control group was 414.65(231,20,729.81)pg/m L and the level of PLCE1 in the disease group was 237.84(116.14,535.85)pg/m L(Z =-3.212,P < 0.001),the value of case group is well below the control group.Conclusion:(1)In this study,all the mutations we found were heterozygous.Five exon mutations(c.578T>C 、c.670C>T、c.923G>T、c.4916C>T、c.5927＿5929del)are considered to be pathogenic mutations.Three exon mutations(c.176C>T、c.389T>C、c.4304C>T)and a splice mutation(c.6885+12C>G)are considered to be potential pathogenic mutations.A total of six newly discovered mutation(c.923G>T 、 c.958T>A 、 c.1151C>T 、 c.2341A>G 、c.3592G>C、c.6885+12C>G)were found.c.923G>T is a pathogenic mutation of the newly discovered PLCE1 gene.(2)It demonstrares the nephritic phenotypes caused by PLCE1 genetic mutation are diverse,they may differ by race and region and are not enough to cause FSGS.(3)PLCE1 protein of serum may act as a protective protein to guarantee various life activities of cells by participating in multiple signal transduction pathways.