Nail-patella syndrome. Overview on clinical and molecular findings

Abstract.

Nail-patella syndrome (NPS) is a rare autosomal dominant pleiotropic disorder characterized by dysplasia of the nails, patellar aplasia or hypoplasia, iliac horns, dysplasia of the elbows, and frequently glaucoma and progressive nephropathy. The recent identification of the causative gene for this syndrome has initiated further studies of the phenotype and molecular pathogenesis of kidney disease in NPS. The gene underlying NPS, LMX1B, is a LIM-homeodomain transcription factor involved in normal patterning of the dorsoventral axis of the limb during development and early morphogenesis of the glomerular basement membrane. Molecular studies of Lmx1b, combined with genetic and immunohistochemical investigation of different alpha chains of type IV collagen in the Lmx1b null mice kidney, a mouse model for NPS, have provided evidence that Lmx1b is involved in the pathogenesis of NPS glomerulopathy. At present evidence for a correlation between the presence and severity of the renal and extrarenal anomalies and LMX1B genotype is lacking. This review focuses on the recent advances in clinical and molecular genetic studies of NPS.