Sixty percent of women with the CLC-5 deletion-insertion had nephrolithiasis, although calcium excretion before and after oral calcium challenge was similar to that in unaffected females.
Dent's disease, an X-linked disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrolithiasis, is due to mutations of the chloride/proton antiporter 5, CLC-5; ADHH is associated with activating mutations of the CaSR, which is a G-protein-coupled receptor; hypophosphatemic hypercalciuric nephrolithiasis associated with rickets is due to mutations in the type 2c sodium-phosphate co-transporter (NPT2c); and familial hypomagnesemia with hypercalciuria is due to mutations of paracellin-1, which is a member of the claudin family of membrane proteins that form the intercellular tight junction barrier in a variety of epithelia.
Dent's disease, an X-linked disorder characterized by low molecular weight proteinuria, hypercalciuria, and nephrolithiasis, is due to mutations of the chloride/proton antiporter, CLC-5; ADHH is associated with activating mutations of the calcium-sensing receptor, which is a G protein-coupled receptor; hypophosphatemic hypercalciuric nephrolithiasis associated with rickets is due to mutations in the type 2c sodium-phosphate cotransporter (NPT2c); and familial hypomagnesemia with hypercalciuria is due to mutations of paracellin-1, which is a member of the claudin family of membrane proteins that form the intercellular tight junction barrier in a variety of epithelia.
Dent's disease (X-linked nephrolithiasis) is a proximal tubulopathy that has been consistently associated with inactivating mutations in the CLCN5 gene encoding the ClC-5 chloride channel expressed in tubular epithelial cells.
In the course of CLCN5 SSCP analysis in patients with hypercalciuric nephrolithiasis, we detected a novel mutation at intron 2 of the CLCN5 gene, a T-to-G substitution, located 17 bp upstream of the AG acceptor site.
The intact hypocalciuric response to a thiazide diuretic indicates that inactivation of the ClC-5 chloride channel does not impair calcium transport in the distal convoluted tubule and indicates that thiazides should be useful in reducing the risk of kidney stone recurrence in patients with Dent's disease.
ClC-5 is a chloride channel whose gene mutations have been reported to be associated with X-linked nephrolithiasis (XRN), X-linked recessive hypophosphatemic rickets (XLRH), Dent disease, and idiopathic low-molecular-weight proteinuria (ILMWP) in Japanese children.
The observations of renal failure in one male and nephrolithiasis in two females represent important new findings in this Japanese variant of Dent's disease that is associated with CLCN5 mutations.
Dent's disease (X-linked nephrolithiasis) is associated with mutations in the CLCN5 chloride channel gene, and low molecular weight (LMW) proteinuria was universally observed in affected males.
Dent's disease, which is a renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrolithiasis, is associated with inactivating mutations of the X-linked chloride channel, CLC-5.
Characterization of novel promoter and enhancer elements of the mouse homologue of the Dent disease gene, CLCN5, implicated in X-linked hereditary nephrolithiasis.
Loss-of-function mutations of the ClC-5 chloride channel lead to Dent's disease, a syndrome characterized by low molecular weight proteinuria, hypercalciuria, and kidney stones.
Mutations in the CLCN5 gene have been demonstrated in three disorders of hypercalciuric nephrolithiasis, i.e., Dent's disease, X-linked recessive nephrolithiasis, and X-linked recessive hypophosphatemic rickets.
Mutations in the CLCN5 gene, mapped in Xp11.22, have been recently reported to be associated with X-linked nephrolithiasis, X-linked recessive hypophosphataemic rickets and Dent's disease.