Infantile steroid-resistant nephrotic syndrome associated with double homozygous mutations of podocin.
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.
Caridi
Gianluca
G
Laboratory on Pathophysiology of Uremia, Istituto Giannina Gaslini, Genoa, Italy.
Berdeli
Afig
A
Dagnino
Monica
M
Di Duca
Marco
M
Mir
Sevgi
S
Cura
Alphan
A
Ravazzolo
Roberto
R
Ghiggeri
Gian Marco
GM
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
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D013256:Steroids