Aims: Steroid-resistant 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 childhood-onset familial SRNS. The present study revealed the genotype of a Chinese pedigree with autosomal recessive (AR) SRNS and reported a novel disease-causing NPHS2 mutation.
Methods: A Chinese pedigree with AR-SRNS was enrolled in the study. All eight exons and exon-intron 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.
Results: A 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.
Conclusions: The compound heterozygous mutation in NPHS2 may explain the development of SRNS in this family. p.Arg71X is a novel disease-causing mutation leading to a deficient expression of podocin.