Pathology vs. molecular genetics: (re)defining the spectrum of Alport syndrome.

Abstract

Next generation sequencing applied to families with glomerular disease has been instrumental in identifying new genes and pathways involved in podocyte homeostasis. Malone et al. performed sequencing on 70 families with FSGS and discovered that 10% had variants in surprising “old” genes, COL4A3 and COL4A4, which are involved in Alport syndrome and thin basement membrane nephropathy. These data show that a subset of renal manifestations associated with COL4A3 or COL4A4 variants cannot be distinguished from FSGS by clinical data or by histopathology. Thus, a diagnosis of FSGS may sometimes fall within the spectrum of Alport syndrome.