Nonfunction of the ECT2 gene may cause renal tubulointerstitial injury leading to focal segmental glomerulosclerosis.

BACKGROUND

Secondary focal segmental glomerulosclerosis (FSGS) follows congenital or acquired tubulointerstitial alterations such as in Dent's disease, Lowe syndrome, and reflux nephropathy. Failure of adequate regeneration after tubulointerstitial injury, or abnormal tubulogenesis, can disturb intrarenal blood circulation, causing excessive glomerular filtration. The epithelial cell-transforming sequence 2 gene (ECT2) contributes to tight junction function in epithelial cells.

METHODS

We encountered two patients with a nonfunctioning ECT2 genotype who later developed FSGS. Both developed proteinuria associated with acute renal failure in early childhood.

RESULTS

Renal biopsy specimens showed marked tubulointerstitial nephritis at the onset of proteinuria, later progressing to FSGS consequent to tubulointerstitial injury. The patients did not respond to corticosteroids and attained only incomplete remission upon cyclosporine A administration. One patient received a maternal renal transplant with good function and no rejection.

CONCLUSIONS

ECT2 is important for tight junction function and maintenance of cell polarity. Nonfunction of this gene may cause renal tubulointerstitial injury, progressing to glomerular sclerosis.