Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement.
Claudins are major components of tight junctions and contribute to the epithelial-barrier function by restricting free diffusion of solutes through the paracellular pathway. We have mapped a new locus for recessive renal magnesium loss on chromosome 1p34.2 and have identified mutations in CLDN19, a member of the claudin multigene family, in patients affected by hypomagnesemia, renal failure, and severe ocular abnormalities. CLDN19 encodes the tight-junction protein claudin-19, and we demonstrate high expression of CLDN19 in renal tubules and the retina. The identified mutations interfere severely with either cell-membrane trafficking or the assembly of the claudin-19 protein. The identification of CLDN19 mutations in patients with chronic renal failure and severe visual impairment supports the fundamental role of claudin-19 for normal renal tubular function and undisturbed organization and development of the retina.
Konrad
Martin
M
University Children's Hospital, Inselspital, Bern, Switzerland. martin.konrad@insel.ch
Schaller
Andre
A
Seelow
Dominik
D
Pandey
Amit V
AV
Waldegger
Siegfried
S
Lesslauer
Annegret
A
Vitzthum
Helga
H
Suzuki
Yoshiro
Y
Luk
John M
JM
Becker
Christian
C
Schlingmann
Karl P
KP
Schmid
Marcel
M
Rodriguez-Soriano
Juan
J
Ariceta
Gema
G
Cano
Francisco
F
Enriquez
Ricardo
R
Juppner
Harald
H
Bakkaloglu
Sevcan A
SA
Hediger
Matthias A
MA
Gallati
Sabina
S
Neuhauss
Stephan C F
SC
Nurnberg
Peter
P
Weber
Stefanie
S
D000293:Adolescent; D000328:Adult; D000818:Animals; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D057167:Claudins; D004285:Dogs; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000235:genetics*; D008275:Magnesium Deficiency / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000235:genetics*
C508912:CLDN19 protein, human; D057167:Claudins; C502666:Cldn19 protein, mouse; D008565:Membrane Proteins; D011994:Recombinant Proteins; C502010:claudin 16