title: Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement.
abstract: 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.
authors.affiliation: University Children's Hospital, Inselspital, Bern, Switzerland. martin.konrad@insel.ch
authors.forename: Martin
authors.initials: M
authors.lastname: Konrad
authors.forename: Andre
authors.initials: A
authors.lastname: Schaller
authors.forename: Dominik
authors.initials: D
authors.lastname: Seelow
authors.forename: Amit V
authors.initials: AV
authors.lastname: Pandey
authors.forename: Siegfried
authors.initials: S
authors.lastname: Waldegger
authors.forename: Annegret
authors.initials: A
authors.lastname: Lesslauer
authors.forename: Helga
authors.initials: H
authors.lastname: Vitzthum
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: John M
authors.initials: JM
authors.lastname: Luk
authors.forename: Christian
authors.initials: C
authors.lastname: Becker
authors.forename: Karl P
authors.initials: KP
authors.lastname: Schlingmann
authors.forename: Marcel
authors.initials: M
authors.lastname: Schmid
authors.forename: Juan
authors.initials: J
authors.lastname: Rodriguez-Soriano
authors.forename: Gema
authors.initials: G
authors.lastname: Ariceta
authors.forename: Francisco
authors.initials: F
authors.lastname: Cano
authors.forename: Ricardo
authors.initials: R
authors.lastname: Enriquez
authors.forename: Harald
authors.initials: H
authors.lastname: Juppner
authors.forename: Sevcan A
authors.initials: SA
authors.lastname: Bakkaloglu
authors.forename: Matthias A
authors.initials: MA
authors.lastname: Hediger
authors.forename: Sabina
authors.initials: S
authors.lastname: Gallati
authors.forename: Stephan C F
authors.initials: SC
authors.lastname: Neuhauss
authors.forename: Peter
authors.initials: P
authors.lastname: Nurnberg
authors.forename: Stefanie
authors.initials: S
authors.lastname: Weber
mesh_terms: 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*
chemical_list: C508912:CLDN19 protein, human; D057167:Claudins; C502666:Cldn19 protein, mouse; D008565:Membrane Proteins; D011994:Recombinant Proteins; C502010:claudin 16