POSITIONALLY CLONED GENE FOR A NOVEL GLOMERULAR PROTEIN - NEPHRIN - IS MUTATED IN CONGENITAL NEPHROTIC SYNDROME

Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autoso mal-recessive disorder, characterized by massive proteinuria in utero and nephrosis at birth. In this study, the 150 kb critical region of N PHS1 was sequenced, revealing the presence of at least 11 genes, the s tructures of 5 of which were determined. Four different mutations segr egating with the disease were found in one of the genes in NPHS1 patie nts. The NPHS1 gene product, termed nephrin, is a 1241-residue putativ e transmembrane protein of the immunoglobulin family of cell adhesion molecules, which by Northern and in situ hybridization was shown to be specifically expressed in renal glomeruli. The results demonstrate a crucial role for this protein in the development or function of the ki dney filtration barrier.