Altered paracellular cation permeability due to a rare CLDN10B variant causes anhidrosis and kidney damage.

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. Anal

SUBMITTER: Klar J 

PROVIDER: S-EPMC5521874 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature