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@ARTICLE{Klar:276855,
      author       = {Klar, Joakim and Piontek, Jörg and Milatz, Susanne and
                      Tariq, Muhammad and Jameel, Muhammad and Breiderhoff, Tilman
                      and Schuster, Jens and Fatima, Ambrin and Asif, Maria and
                      Sher, Muhammad and Mäbert, Katrin and Fromm, Anja and Baig,
                      Shahid M. and Günzel, Dorothee and Dahl, Niklas},
      title        = {{A}ltered paracellular cation permeability due to a rare
                      {CLDN}10{B} variant causes anhidrosis and kidney damage},
      journal      = {PLoS Genetics},
      volume       = {13},
      number       = {7},
      issn         = {1553-7390},
      address      = {San Francisco, Calif.},
      publisher    = {Public Library of Science},
      reportid     = {DZNE-2025-00368},
      pages        = {e1006897},
      year         = {2017},
      abstract     = {Claudins constitute the major component of tight junctions
                      and regulate paracellular permeability of epithelia.
                      Claudin-10 occurs in two major isoforms that form
                      paracellular channels with ion selectivity. We report on two
                      families segregating an autosomal recessive disorder
                      characterized by generalized anhidrosis, severe heat
                      intolerance and mild kidney failure. All affected
                      individuals carry a rare homozygous missense mutation
                      c.144C>G, p.(N48K) specific for the claudin-10b isoform.
                      Immunostaining of sweat glands from patients suggested that
                      the disease is associated with reduced levels of claudin-10b
                      in the plasma membranes and in canaliculi of the secretory
                      portion. Expression of claudin-10b N48K in a 3D cell model
                      of sweat secretion indicated perturbed paracellular Na+
                      transport. Analysis of paracellular permeability revealed
                      that claudin-10b N48K maintained cation over anion
                      selectivity but with a reduced general ion conductance.
                      Furthermore, freeze fracture electron microscopy showed that
                      claudin-10b N48K was associated with impaired tight junction
                      strand formation and altered cis-oligomer formation. These
                      data suggest that claudin-10b N48K causes anhidrosis and our
                      findings are consistent with a combined effect from
                      perturbed TJ function and increased degradation of
                      claudin-10b N48K in the sweat glands. Furthermore, affected
                      individuals present with Mg2+ retention, secondary
                      hyperparathyroidism and mild kidney failure that suggest a
                      disturbed reabsorption of cations in the kidneys. These
                      renal-derived features recapitulate several phenotypic
                      aspects detected in mice with kidney specific loss of both
                      claudin-10 isoforms. Our study adds to the spectrum of
                      phenotypes caused by tight junction proteins and
                      demonstrates a pivotal role for claudin-10b in maintaining
                      paracellular Na+ permeability for sweat production and
                      kidney function.},
      ddc          = {610},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1371/journal.pgen.1006897},
      url          = {https://pub.dzne.de/record/276855},
}