Disheveled associated activator of morphogenesis 2 variants may produce alport-like changes: a case report.

backgroundDAAM2 is an important formin, which plays an important role in the polymerization of monomeric actin into linear filaments. Previous studies have suggested that the DAAM2 variant mainly causes congenital Nephrotic Syndrome Type 24 (NPHS24), which is characterized by focal segmental glomerulosclerosis and steroid resistant nephrotic syndrome.

methodsWe report a case of a young man diagnosed with IgA nephropathy by renal biopsy.

resultsSpecifically, in addition to IgA nephropathy, this patient also had diffuse thinning of GBM, reduced segmental expression of type IV collagen α3 in the glomerulus, and binocular keratoconus which is consistent with features of Alport syndrome. However, whole exon sequencing eliminated the common variation in the type IV collagen-encoding gene and revealed a homozygous mutation in the formin homology 2 (FH2) domain of DAAM2, the core domain responsible for actin polymerization.

conclusionIn conclusion, our case suggests that the spectrum of DAAM2-associated nephropathies might be broader than previously recognized. We propose the novel hypothesis that mutations in the FH2 domain of DAAM2 could predispose to an Alport-like phenotype, potentially through cytoskeletal dysregulation affecting glomerular basement membrane (GBM) integrity. This expands the potential clinical heterogeneity linked to DAAM2 and warrants further investigation.