Clinical features and mutational survey of NPHS2 (podocin) in Japanese children with focal segmental glomerulosclerosis who underwent renal transplantation.

Recurrent FSGS is a major challenge in the field of nephrology. To clarify the role of NPHS2 defects in the pathogenesis of FSGS recurrence, we sequenced all eight exons of NPHS2 in 11 Japanese pediatric FSGS patients with or without post-transplant recurrence. All patients had biopsy-proven primary FSGS, had no family history of renal diseases or consanguinity, were steroid-resistant, and received living-related renal transplantation. The mean age at onset was 5.0 +/- 3.1 yr and mean age at renal transplantation was 10.4 +/- 4.1 yr. Mutational analysis of NPHS2 was performed using polymerase chain reaction and direct sequencing. We found a synonymous T/C polymorphism at alanine 318 (GCC to GCT) in seven of 11 patients but no other causative NPHS2 mutations. FSGS recurred immediately after transplant in seven patients, while the remaining four patients had no recurrence for 3.2-5.8 yr. There were no differences between recurrent and non-recurrent patients in the onset age and the interval from onset to ESRD. In conclusion, we detected no causative NPHS2 mutations in Japanese pediatric FSGS patients with or without post-transplant recurrence. Further studies on the involvement of other genes are required to better understand recurrent FSGS.