title: Infantile steroid-resistant nephrotic syndrome associated with double homozygous mutations of podocin.
abstract: Mutations of NPHS2, ie, the gene coding for podocin, are associated with nephrotic syndrome (NS) in children, with a clinical phenotype characterized by variable age at onset (from 1 to 10 years) and steroid/cyclosporine resistance. The authors describe an infantile variant in 2 families (3 patients) from Turkey, characterized by homozygosity of a complex haplotype, in which 2 podocin mutations (P20L-R168H) are present in cis. It results from the insertion of a new mutation (R168H), only found in Turkey, on a more ancient haplotype containing the P20L mutation observed in the European population. All patients described had presented with NS within the first 6 months of life with strict resistance to drugs and a histologic background of focal segmental glomerulosclerosis. This is the first description of double homozygous mutations in an autosomal recessive renal disease reported in the literature. The association with infantile NS widens the panel of clinical presentation related to NPHS2 mutations.
authors.affiliation: Laboratory on Pathophysiology of Uremia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.forename: Afig
authors.initials: A
authors.lastname: Berdeli
authors.forename: Monica
authors.initials: M
authors.lastname: Dagnino
authors.forename: Marco
authors.initials: M
authors.lastname: Di Duca
authors.forename: Sevgi
authors.initials: S
authors.lastname: Mir
authors.forename: Alphan
authors.initials: A
authors.lastname: Cura
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
mesh_terms: D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009404:Nephrotic Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D013256:Steroids / Q000627:therapeutic use; D014421:Turkey
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D013256:Steroids