Fibronectin Glomerulopathy: An Unusual Cause of Adult-Onset Nephrotic Syndrome

We report the case of a 50-year-old woman with nephrotic-range proteinuria and lobular glomerulopathy on kidney biopsy. Homogenous glomerular deposits were non-immune reactive, but immunofluorescence microscopy for fibronectin was strongly positive. Ultrastructurally, the deposits were granular with focal fibril formation, leading to a diagnosis of fibronectin glomerulopathy. Mutational analysis revealed a heterozygous missense mutation in fibronectin (leading to the tyrosine at amino acid 973 being replaced by cysteine [Y973C]), confirming the diagnosis. This mutation affects Hep-III, one of the heparin-binding domains of fibronectin, and results in functional abnormalities.