claudin19

Claudin-19 is a member of the claudin family of integral membrane proteins that form tight junctions between adjacent cells. It is encoded by the CLDN19 gene in humans and contributes to the paracellular barrier and selective ion permeability of epithelial and endothelial layers. Claudin-19 typically functions together with other claudins to create tight junction strands that regulate the diffusion of ions, including magnesium and calcium, across epithelia.

Expression and function: In the kidney, CLDN19 is present in segments such as the thick ascending limb of the loop of Henle and distal tubules, where it interacts with claudin-16 (CLDN16) to facilitate magnesium and calcium reabsorption. In the retina and possibly other tissues, claudin-19 participates in barrier properties essential for tissue integrity and homeostasis; disruption of these functions can contribute to ocular abnormalities.

Genetic disorders: Pathogenic variants in CLDN19 are associated with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) type 2. Affected individuals typically exhibit hypomagnesemia with increased urinary magnesium excretion and hypercalciuria, and they may develop nephrocalcinosis. Retinal involvement, including retinal dystrophy or other ocular defects, is a notable feature that can accompany the renal phenotype, distinguishing CLDN19-related disease from CLDN16-related forms.

Diagnosis and management: Diagnosis is supported by clinical features and confirmed through CLDN19 genetic testing. Laboratory assessment often shows low serum magnesium with elevated urinary excretion of magnesium and calcium. Imaging can reveal nephrocalcinosis. Management focuses on magnesium supplementation, electrolyte balance, monitoring of kidney function, treatment of ocular symptoms, and genetic counseling for affected families.

See also: Claudins; tight junctions; FHHNC.