We report a case of nail-patella syndrome (NPS) with unusual thinning of the glomerular basement membrane (GBM) associated with a novel heterozygous variant in the LMX1B gene. A 43-year-old female patient with a previous diagnosis of NPS, referred to our hospital for persistent proteinuria, underwent a renal biopsy, which revealed minor glomerular abnormalities. She underwent a second renal biopsy at the age of 56 owing to the presence of persistent proteinuria and decline in serum albumin, meeting the diagnostic criteria for nephrotic syndrome. Light microscopy demonstrated glomerulosclerosis and cystic dilatation of the renal tubules. Notably, electron microscopy revealed unusual thinning of the GBM, which is quite different from typical biopsy findings observed in patients with NPS, characterized by thick GBM with fibrillary material and electron-lucent structures. Comprehensive genetic screening for 168 known genes responsible for inherited kidney diseases using a next-generation sequencing panel identified a novel heterozygous in-frame deletion-insertion (c.723_729delinsCAAC: p.[Ser242_Lys243delinsAsn]) in exon 4 of the LMX1B gene, which may account for the disrupted GBM structure. Further studies are warranted to elucidate the complex genotype-phenotype relationship between LMX1B and proper GBM morphogenesis.
Keywords: Glomerular basement membrane; Glomerulosclerosis; LMX1B variant; Podocyte foot process effacement; Proteinuria.
© 2021 S. Karger AG, Basel.