OBJECTIVEMutations in NPHS2 mapped to 1q25-q31 and encoding podocin, which is exclusively expressed in glomerular podocytes, are responsible for autosomal recessive familial steroid-resistant nephrotic syndrome (SRNS) with minor glomerular abnormalities or focal segmental glomerulosclerosis. Different groups from European and North American countries have screened NPHS2 mutations in familial SRNS with recessive inheritance, documenting a mutation detection rate of 45% - 55% in families. This study aimed to examine mutations in the NPHS2 gene in Southern Chinese Han ethnic group patients with familial SRNS.

METHODSGenomic DNA from 3 probands from Southern Chinese Han families with autosomal recessive SRNS, and their siblings and parents was isolated and analyzed for all eight exons, exon-intron boundaries and promoter of NPHS2 using the polymerase chain reaction and direct sequencing.

RESULTSNo mutation of NPHS2 in all eight exons and exon-intron boundaries was identified in the 3 probands. However, a polymorphism of 954T > C in exon 8 was detected in all the 3 probands and some controls, and 5 variants of NPHS2 promoter, -1709G > A, -1000A > T, -670C > T, -116C > T and -51G > T, were identified in some patients and controls, indicating that these variants are polymorphisms. One heterozygous variant of NPHS2 promoter, -1715A > G, was also identified in one proband and her mother whose urinalyses were normal, whereas it was not found in any of the 50 controls. There was no significant difference in the allelic frequencies of -1709G > A, -1000A > T, -670C > T, -116C > T and -51G > T polymorphisms between the patients and controls.

CONCLUSIONNPHS2 mutations are not a major cause of familial steroid-resistant nephrotic syndrome in Southern Chinese Han ethnic group included in the study.