Analysis of NPHS2 mutations in Turkish steroid-resistant nephrotic syndrome patients

Abstract

Mutations in the NPHS2 gene are a frequent cause of familial and sporadic steroid-resistant nephrotic syndrome (SRNS). Inter-ethnic differences have also been suggested to affect the incidence of these mutations. The frequency and spectrum of podocin mutations in the Turkish population have remained largely unknown. As such, the aim of this study was to screen for podocin mutations in Turkish patients with SRNS. Thirty two patients from 30 unrelated families with SRNS were examined. There were seven familial cases from five different families and 25 sporadic cases. PCR-single-strand conformation polymorphism (SSCP) analysis of the NPHS2 gene was followed by direct sequencing. Five different NPHS2 mutations were detected in four of the 30 (13.3%) families studied; five familial patients from three unrelated families (60%) and one sporadic case (4%) were found to carry podocin mutations. The detected mutations included homozygous c. 419delG, compound heterozygous p. [Arg238Ser] + [Pro118Leu], homozygous p. [Pro20Leu; Arg168His] and heterozygous p. Pro20Leu. Two siblings with compound heterozygous mutations had been reported previously by our group. Podocin mutations were found to be responsible for some of the SRNS cases in Turkey, especially when there was more than one affected person in the family. Our results also suggest the presence of a wide range of phenotypic variability between individuals with the same genotype.