Familial membranous nephropathy: an X-linked genetic susceptibility?

Abstract

Background: Membranous nephropathy (MN) is the most common histological diagnosis in adults with nephrotic syndrome and a leading cause of end-stage kidney failure from glomerulonephritis. Little is known about the underlying aetiology, although anti-glomerular antibodies have been implicated. No specific underlying genetic defect has yet been identified.

Methods: In a family with four members in three generations affected by primary MN, the serum of affected members and their mothers were assessed for anti-glomerular antibodies.

Results: All four affected are male and connected through the maternal line, indicative of X-linked inheritance. Age of onset of nephrotic syndrome varied between 1 and 67 years of age, suggesting that a potential underlying gene may confer a genetic predisposition to MN, but other factors, genetic or environmental, are necessary to trigger the disease. Serologic studies revealed antibodies against glomerular and peritubular endothelial cells in the mother of the youngest patient.

Conclusions: We have identified the largest reported family with a potential X-linked susceptibility to MN. Foeto-maternal alloimmunization may have triggered the disease in the youngest individual. Considering that the majority of patients with sporadic MN are male, identification of an X-linked predisposing factor may have implications well beyond this family and could provide a target for treatment.