The nephrotic syndrome refers to a genetically heterogeneous group of disorders characterized by proteinuria, hypoalbuminemia, and edema, resulting in end-stage kidney disease if untreated. Inherited defects in podocyte structure and function have been observed in some children with ... The nephrotic syndrome refers to a genetically heterogeneous group of disorders characterized by proteinuria, hypoalbuminemia, and edema, resulting in end-stage kidney disease if untreated. Inherited defects in podocyte structure and function have been observed in some children with the steroid-resistant subtype of nephrotic syndrome (summary by Ozaltin et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Ozaltin et al. (2011) reported a consanguineous Turkish family in which 2 sibs had onset of nephrotic syndrome at ages 7 and 5 years, respectively. Both had proteinuria and decreased serum albumin. Both were initially steroid-resistant, but showed ... Ozaltin et al. (2011) reported a consanguineous Turkish family in which 2 sibs had onset of nephrotic syndrome at ages 7 and 5 years, respectively. Both had proteinuria and decreased serum albumin. Both were initially steroid-resistant, but showed partial responses to combined therapy. Neither had developed end-stage renal disease by ages 11 and 7 years. Renal biopsy of 1 patient showed focal segmental glomerulosclerosis and mild focal tubulointerstitial fibrosis and atrophy, but no cellular proliferation or matrix expansion. Electron microscopy showed diffuse foot process effacement and widespread attenuation of the glomerular basement membranes without thickening. The podocytes appeared swollen and vacuolated. Ozaltin et al. (2011) identified a second consanguineous Turkish family with the same phenotype in 3 sibs. One sib presented at age 14 years and had no response to steroid treatment. She progressed to end-stage renal disease at age 18 years and received a living-related kidney transplant with no disease recurrence. The other 2 sibs were diagnosed while clinically asymptomatic, at ages 9 and 11 years, respectively. One had partial response to combined therapy, whereas the other initially achieved complete remission with oral prednisone, but later became steroid-dependent and had a relapse. At ages 15 and 12 years, respectively, their glomerular filtration rates were normal, although both had proteinuria. Renal biopsy of 1 patient yielded a pathologic diagnosis of minimal change disease. There was global sclerosing of 3 of 38 glomeruli with narrow zones of interstitial fibrosis and tubular atrophy around the globally sclerosed glomeruli. Electron microscopy showed diffuse foot process fusion and extensive microvillus transformation of the podocytes.
By homozygosity mapping followed by candidate gene sequencing of a consanguineous Turkish family with nephrotic syndrome, Ozaltin et al. (2011) identified a homozygous splice site mutation in the PTPRO gene (600579.0001). Analysis of this gene in 17 additional ... By homozygosity mapping followed by candidate gene sequencing of a consanguineous Turkish family with nephrotic syndrome, Ozaltin et al. (2011) identified a homozygous splice site mutation in the PTPRO gene (600579.0001). Analysis of this gene in 17 additional families found another homozygous mutation in a second consanguineous Turkish family (600579.0002). The oldest sib in this family, who had the most severe phenotype necessitating renal transplant, also carried a heterozygous mutation in the podocin gene (R229Q; 604766.0011), which was thought to exacerbate the clinical picture.