Chinese Medical E-ournals Database

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2013, Vol. 09 ›› Issue (03): 323 -329. doi: 10.3877/cma.j.issn.1673-5250.2013.03.010

Special Issue:

Original Article

Causes Analysis of 36 Children With Focal Segmental Glomerulosclerosis

Guo­min LI1, Hong XU1(), Yi­hui ZHAI2, Xue­wu GAO1, qian SHEN1, Xiao­e ZHAO1, Yu AN2, Xiao­yan FANG1   

  1. 1. Children's Hospital of Fudan University, Shanghai 201102, China
  • Received:2013-04-16 Revised:2013-05-07 Published:2013-06-01
  • Corresponding author: Hong XU
  • About author:
    (Corresponding author: XU Hong, Email: )
Objective

To investigate the causes of children with focal segmental glomerulosclerosis(FSGS).

Methods

From January 1979 to December 2011, 36 clinical data of FSGS children who took renal biopsy were included in the study, and their clinical features were analyzed retrospectively. Sequencing of all NPHS2 exons, WT1 exon 8, 9 and analysis of 42 mutation spots about NPHS1, CD2AP, PLCε1, APOL1, TRPC6, INF2, MYH9 and MYO1E by Snapshot technology were performed in follow-up patients with unknown cause FSGS. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Children's Hospital of Fudan University.

Results

There were 10 FSGS children with clear causative lesion(27.8%), which were low birth weight infants(LBWI, 2 cases), minimal change disease(MCD, 2 cases), hepatitis C(1 case), vesicoureteral reflux(VUR, 1 case), Galloway-Mowat syndrome (GMS, 1 case), Denys-Drash syndrome (DDS, 1 case), IgA nephropathy (1 case)and familial FSGS (1 case). There were 26 FSGS children with unknown cause(72.2%). Gene and its mutation analysis were conducted in 6 follow-up FSGS children with unknown cause and 1 DDS children.2 children (including 1 DDS child) have WTI mutations which were both heterozygous ARG394TRP mutation.

Conclusions

Causes of FSGS are diverse, LBWI is one of the important causes of FSGS. FSGS children with unknown cause are still the majority, but pathogenic mutations may be found by gene analysis in these patients.We should use genetic molecular techniques to analyze unknown causes of FSGS in children.

表1 8个基因共计42个相关突变位点
Table 1 42 position of mutations in 8 genes
表2 10例病因明确FSGS患儿的临床特点
Table 2 Clinical features of 10 FSGS patients with clear causative lesion
图1 2例WT1突变图(箭头示突变位点)
Figure 1 Sequencing of WT1 exon 8, 9(The arrows indicate mutant positions)
表3 6例坚持随访且病因不明FSGS患儿临床特点和基因突变位点结果
Table 3 Clinical features and position of mutations of 6 FSGS patients with unknown cause
表4 2例WT1突变患儿临床特点
Table 4 Clinical features of 2 WT1 mutations patients
[1]
Collins AJ, Foley RN, Herzog C, et al.US renal data system 2010 annual data report[J]. Am J Kidney Dis, 2011, 57(1):1-526.
[2]
Heeringa SF, Gbadegesin R, et al. Low prevalence of NPHS2 mutations in African American children with steroid-resistant nephrotic syndrome[J]. Pediatr Nephrol, 2008, 23(9):1455-1460.
[3]
Kitiyakara C, Eggers P, Kopp JB, et al. Twenty-one-year trend in ESRD due to focal segmental glomerulosclerosis in the United States[J]. Am J Kidney Dis, 2004, 44(5):815-825.
[4]
Gipson DS, Chin H, Presler TP, et al. Differential risk of remission and ESRD in childhood FSGS[J]. Pediatr Nephrol, 2006, 21(3):344-349.
[5]
Conlon PJ, Lynn K, Winn MP, et al.Spectrum of disease in familial focal and segmental glomerulosclerosis[J].Kidney Int, 1999, 56(5):1863-1871.
[6]
Lowik MM, Groenen PJ, Levtchenko EN, et al. Molecular genetic analysis of podocyte genes in focal segmental glomerulosclerosis:A review[J].Eur J Pediatr, 2009, 168(11):1291-304.
[7]
Saleem MA.New developments in steroid-resistant nephrotic syndrome[J].Pediatr Nephrol, 2012, 28(5):699-709.
[8]
Zenker M, Machuca E, Antignac C. Genetics of nephrotic syndrome: New insights into molecules acting at the glomerular filtration barrier[J].J Mol Med (Berl), 2009, 87(9):849-857.
[9]
Piscione TD, Licht C.Genetics of proteinuria:An overview of gene mutations associated with nonsyndromic proteinuric glomerulopathies[J].Adv Chronic Kidney Dis, 2011, 18(4):273-289.
[10]
Gubler MC.Nephrotic syndrome:Genetic testing in steroid-resistant nephrotic syndrome[J]. Nat Rev Nephrol, 2011, 7(8):430-431.
[11]
D'Agati VD, Fogo AB, Bruijn JA, et al. Pathologic classification of focal segmental glomerulosclerosis: A working proposal[J]. Am J Kidney Dis, 2004, 43(2):368-382.
[12]
Xu R, Zuo L. Low birthweight and chronic kidney disease[J].Nephrology (Carlton), 2010, 15(2):18-22.
[13]
Hodgin JB, Rasoulpour M, Markowitz GS, et al. Very low birth weight is a risk factor for secondary focal segmental glomerulosclerosis[J].Clin J Am Soc Nephrol, 2009, 4(1):71-76.
[14]
Jeong HJ, Kim YS, Kwon KW, et al. Segmental glomerulosclerosis in IgA nephropathy after renal transplantation: Relationship with proteinuria and therapeutic response to enalapril[J]. Clin Transplant, 2003, 17(2):108-113.
[15]
Vizjak A, Ferluga D, Rozic M, et al. Pathology, clinical presentations, and outcomes of C1q nephropathy[J]. J Am Soc Nephrol, 2008, 19(11):2237-2244.
[16]
Shrestha S, Sumingan N, Tan J, et al. Henoch Schonlein purpura with nephritis in adults: Adverse prognostic indicators in a UK population[J]. QJM, 2006, 99(4):253-265.
[17]
Kraft SW, Schwartz MM, Korbet SM, et al. Glomerular podocytopathy in patients with systemic lupus erythematosus[J].J Am Soc Nephrol, 2005, 16(1):175-179.
[18]
Tanaka H, Waga S, Nakahata T, et al.Acute glomerulonephritis superimposed on focal segmental glomerulosclerosis: A case report[J]. Tohoku J Exp Med, 2000, 191(3):177-181.
[19]
Ahmad H, Tejani A. Predictive value of repeat renal biopsies in children with nephrotic syndrome[J].Nephron, 2000, 84(4):342-436.
[20]
Wyatt CM, Meliambro K, Klotman PE. Recent progress in HIV-associated nephropathy[J].Annu Rev Med, 2012, 63(1):147-159.
[21]
Moudgil A, Nast CC, Bagga A, et al. Association of parvovirus B19 infection with idiopathic collapsing glomerulopathy[J].Kidney Int, 2001, 59(6):2126-2133.
[22]
Chirumamilla SR, He C, Racusen LC, et al. Acute kidney injury in a girl with ulcerative colitis and cytomegalovirus-induced focal segmental glomerular sclerosis[J].World J Pediatr, 2011, 7(2):223-225.
[23]
Khaira A, Upadhyay BK, Sharma A, et al. Hepatitis B virus associated focal and segmental glomerular sclerosis: Report of two cases and review of literature[J]. Clin Exp Nephrol, 2009, 13(4):373-377.
[24]
Sakai K, Morito N, Usui J, et al. Focal segmental glomerulosclerosis as a complication of hepatitis B virus infection[J].Nephrol Dial Transplant, 2010, 24(11):1562-1568.
[25]
Stehman-Breen C, Alpers CE, Fleet WP, et al. Focal segmental glomerular sclerosis among patients infected with hepatitis C virus[J].Nephron, 1999, 81(1):37-40.
[26]
Motta M, Malaguarnera M, Restuccia N, et al. Focal segmental glomerulosclerosis and hepatitis C virus: A case report[J].Panminerva Med, 2001, 43(1):49-52.
[27]
Kestil M, Lenkkeri U, Mnnikk M, et al. Positionally cloned gene for a novel glomerular protein—nephrin is mutated in congenital nephrotic syndrome[J]. Mol Cell, 1998, 1(4):575-582.
[28]
Ozaltin F, Ibsirlioglu T, Taskiran EZ, et al. Disruption of PTPRO causes childhood-onset nephrotic syndrome[J].Am J Hum Genet, 2011, 89(1):139-147.
[29]
Hinkes BG, Mucha B, Vlangos CN, et al. Nephrotic syndrome in the first year of life: Two thirds of cases are caused by mutations in 4 genes (NPHS1, NPHS2, WT1, and LAMB2)[J]. Pediatrics, 2007, 119(4):907-919.
[30]
Sako M, Nakanishi K, Obana M, et al. Analysis of NPHS1, NPHS2, ACTN4, and WT1 in Japanese patients with congenital nephrotic syndrome[J].Kidney Int, 2005, 67(4):1248-1255.
[31]
Lee JH, Han KH, Lee H, et al. Genetic basis of congenital and infantile nephrotic syndromes[J].Am J Kidney Dis, 2011, 58(6):1042-1043.
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