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 autosomal-recessive disorder, characterized by massive proteinuria in utero and nephrosis at birth. In this study, the 150 kb critical region of NPHS1 was sequenced, revealing the presence of at least 11 genes, the structures of 5 of which were determined. Four different mutations segregating with the disease were found in one of the genes in NPHS1 patients. The NPHS1 gene product, termed nephrin, is a 1241-residue putative 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 kidney filtration barrier.
Kestilä
M
M
Department of Biochemistry, University of Oulu, Finland.
Lenkkeri
U
U
Männikkö
M
M
Lamerdin
J
J
McCready
P
P
Putaala
H
H
Ruotsalainen
V
V
Morita
T
T
Nissinen
M
M
Herva
R
R
Kashtan
C E
CE
Peltonen
L
L
Holmberg
C
C
Olsen
A
A
Tryggvason
K
K
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D003360:Cosmids; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000302:isolation & purification; D005091:Exons / Q000235:genetics; D005192:Family Health; D017353:Gene Deletion; D015870:Gene Expression; D006239:Haplotypes; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000503:physiopathology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000235:genetics*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D018076:DNA, Complementary; D007136:Immunoglobulins; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; C113267:nephrin