Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement


Konrad M., Schaller A., Seelow D., Pandey A. V. , Waldegger S., Lesslauer A., ...Daha Fazla

AMERICAN JOURNAL OF HUMAN GENETICS, cilt.79, sa.5, ss.949-957, 2006 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 79 Konu: 5
  • Basım Tarihi: 2006
  • Doi Numarası: 10.1086/508617
  • Dergi Adı: AMERICAN JOURNAL OF HUMAN GENETICS
  • Sayfa Sayıları: ss.949-957

Özet

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.