title: [Heterozygotic mutation in NPHS2 gene as a cause of familial steroid resistant nephrotic syndrome in two siblings--case report].
abstract: Within recent years the number of children with focal segmental glomerulonephritis (FSGS) has increased. A significant progress in defining of molecular basis of the disease has been made. Gene mutations for nephrin, podocin, WT1, alpha-actinin 4 cause the damage of filtration barrier of glomerulus and proteinuria in consequence. A girl (S.G.) became ill at the age of 3.5, suffering form steroid-resistant nephritic syndrome (SRNS) with microscopic hematuria. The renal biopsy showed FSGS accompanied by a complete diffuse effacement of podocyte food processes. Despite intensive and regular immunosuppressive therapy, remission was not achieved. In the control renal biopsy performed a year after cyclosporin A had been applied, 50% of globally sclerosed glomeruli as well as some features of post-cyclosporin damage were found. The girl required renal replacement therapy at the age of 10.5. Dialyzed at the adult dialysis centre she died at the age of 11.5. A boy S.P. was diagnosed with SRNS when he was 11.5 years old. The renal biopsy was performed after one month of treatment and showed mesangial proliferation and diffuse effacement of podocyte food processes. After chlorambucil treatment remission was not achieved, and after methylprednisolon pulse therapy only the reduction of proteinuria was achieved. In a control renal biopsy 10 out of 13 glomeruli were globally sclerosed. At the age of 17 the patient showed chronic renal failure with a fast progression of the disease. In September 2000 the boy started renal replacement therapy, an in June 2001 he received a renal transplant without the recurrence of FGS. In 2001 a heterozygous mutation (A284V) in gene NPHS2 was found in both of the siblings. Within the confines of the clinical project ESCAPE Trial another genetic examination was performed. In the boy one missense mutation on one allele (A284V) and the R229Q polymorphism on the other allele were found. In this family the father is bear. ing the A284V mutation and the mother the R229Q variant. These results prove that this disease is due to alterations of the podocin gene in the described family.
authors.affiliation: Collegium Medicum, Uniwersytetu Jagiellońskiego w Krakowie. dadrozdz@cm-uj.krakow.pl
authors.forename: Dorota
authors.initials: D
authors.lastname: Drozdz
authors.forename: Jacek A
authors.initials: JA
authors.lastname: Pietrzyk
authors.forename: Ewa
authors.initials: E
authors.lastname: Wierzchowska-Słowiaczek
authors.forename: Krystyna
authors.initials: K
authors.lastname: Sancewicz-Pach
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
authors.forename: Witold
authors.initials: W
authors.lastname: Miezyński
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D005260:Female; D006579:Heterozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D016030:Kidney Transplantation; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000235:genetics* / Q000628:therapy; D010375:Pedigree; D035781:Siblings; D013256:Steroids / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D013256:Steroids