A novel mutation in NPHS2 gene identified in a Chinese pedigree with autosomal recessive steroid-resistant nephrotic syndrome

SummaryAimsSteroidresistant nephrotic syndrome (SRNS) is an inherent deficiency of podocyte caused by mutations of genes encoding slit diaphragm proteins. Mutations in NPHS2, encoding podocin, have been identified as responsible for childhoodonset familial SRNS. The present study revealed the genotype of a Chinese pedigree with autosomal recessive (AR) SRNS and reported a novel diseasecausing NPHS2 mutation.MethodsA Chinese pedigree with ARSRNS was enrolled in the study. All eight exons and exonintron boundaries of NPHS2 genes were amplified from the genomic DNA of the family members and analysed by direct sequencing. The deficient expression of the mutant protein was illustrated by indirect immunofluorescence.ResultsA compound heterozygous NPHS2 mutation (c.211C > T /c.460dupT) was found in the proband. The paternal c.211C > T is a novel point mutation, resulting in an immediate stop codon (p.Arg71X). The maternal c.460dupT is a frameshift mutation introducing an earlier stop codon (p.Phe156AspfsX10). Both mutations could be expected to lead to truncated protein of podocin. Abnormal expression and distribution of the mutated protein were also exhibited in the patient.ConclusionsThe compound heterozygous mutation in NPHS2 may explain the development of SRNS in this family. p.Arg71X is a novel diseasecausing mutation leading to a deficient expression of podocin.