Wilms′ tumour 1 gene mutations in south Indian children with steroid-resistant nephrotic syndrome

Abstract

Background & objectives:Clinically, nephrotic syndrome (NS) is a diverse group of symptoms; about 20 per cent of NS cases are resistant to steroid treatment, and within ten years they progress to end-stage renal disease. The present study was undertaken to identify the mutations of Wilms’ tumour 1 (WT1) gene in steroid-resistant NS (SRNS) children.Methods:A total of 173 children with SRNS and 100 children in the control group were enrolled in the study. DNA extraction was done, screened for WT1 (exons 8 and 9) gene amplified by polymerase chain reaction and direct sequencing. Karyotype analyses were done for WT1 mutation cases.Results:WT1 mutations were found in three of 173 SRNS cases (2 girls, 1 boy). All of them had intron 9 (IVS 9 + 4 C>T, 2; IVS + 5 G>A, 1) mutation. Of these three cases, one had familial and another two had sporadic history. Renal histology analysis showed two cases with focal segmental glomerulosclerosis (FSGS) and they had external female genitalia but 46, XY karyotype. Both of them had streak gonads. Of the three cases, one expired.Interpretation & conclusions:The findings of the present study indicate that all females with SRNS-FSGS should be screened for WT1 gene mutation to diagnose whether they have FS for possible gonadectomy.

Targeted gene panel for genetic testing of south Indian children with steroid resistant nephrotic syndrome

“…However, reports from India including from our center showed that the prevalence of NPHS2 mutations is much lower in Indian population when compared with Europe and North American population [4% vs. 10.5–28%)] [ 7 – 12 ]. Kumar et al, reported low prevalence of WT1 mutation in south Indian population, whereas we did not detect any mutation in WT1 gene in 100 SRNS children [ 13 , 14 ]. These data suggest that a traditional genetic testing using an algorithmic approach based on age of onset of NS to prioritize the genes to be sequenced by Sanger may not be useful [ 15 , 16 ].…”

Systematic Review of Genotype-Phenotype Correlations in Frasier Syndrome

“…Genetic and clinical data were obtained from a total of 126 cases: 115 cases described in previous reports 6 , 11 , 12 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 and 11 cases diagnosed at our institution ( Table 2 ). There were no significant differences in the proportions of patients with female external genitalia and XY chromosomes between the 2 major variants: c.1432+4 C>T (44/49, 90%) and c.1432+5 G>A (30/35, 86%) ( Table 2 , P = 0.57, χ 2 test).…”