OBJECTIVETo study the clinical features and gene mutations of 4 Chinese children with Dent disease.

METHODSThe clinical and laboratory data of 4 children with Dent disease were analyzed retrospectively. Genetic testing of the 4 cases was carried out.

RESULTSAll of 4 cases were boys. The first impression of Cases 1-3 was Fanconi syndrome. Proteinuria was presented as the first impression in Case 4. All 4 boys presented with low-molecular weight proteinuria (LMWP) and hypercalciuria, including 3 cases with hematuria, 1 case with kidney stones, 2 cases with nephrocalcinosis, 3 cases with hypophosphatemia, and 3 cases with rickets. Mutations of the CLCN5 gene were revealed in three patients (Cases 1, 2 and 4), including exon 6-7del, c.785_787de l(p.263del Leu) and c.1039 C>T (p.Arg347Term). The first two gene mutations had never reported before.

CONCLUSIONSUrine protein electrophoresis should be carried out for patients with proteinuria. Dent disease should be taken into consideration when patients with Fanconi syndrome have hypercalciuria, nephrocalcinosis or kindey stones. Genetic analyses are needed for a definite diagnosis.

Child ; Child, Preschool ; Chloride Channels ; genetics ; Dent Disease ; drug therapy ; genetics ; Humans ; Mutation ; Phosphoric Monoester Hydrolases ; genetics

It is well known that proteins present in the primary urine are reabsorbed in the renal proximal tubules, and that this reabsorption is mediated via the megalincubilin complex and the neonatal Fcgamma receptor. However, the reabsorption is also thought to be influenced by an electrostatic interaction between protein molecules and the microvilli of the renal proximal tubules. By analyzing the charge diversity of urinary IgG, we showed that this reabsorption process occurs in a cationic charge-preferential manner. The charge-selective molecular sieving function of the glomerular capillary walls has long been a target of research since Brenner et al. demonstrated the existence of this function by a differential clearance study by using the anionic dextran sulfate polymer. However, conclusive evidence was not obtained when the study was performed using differential clearance of serum proteins. We noted that immunoglobulin (Ig) A and IgG have similar molecular sizes but distinct molecular isoelectric points. Therefore, we studied the differential clearance of these serum proteins (clearance IgA/ clearance IgG) in podocyte diseases and glomerulonephritis. In addition, we studied this differential clearance in patients with Dent disease rather than in normal subjects because the glomerular sieving function is considered to be normal in subjects with Dent disease. Our results clearly showed that the charge-selective barrier is operational in Dent disease, impaired in podocyte disease, and lacking in glomerulonephritis.
Blood Proteins ; Capillaries ; Child Health ; Dent Disease ; Dextran Sulfate ; Glomerulonephritis ; Humans ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulins ; Isoelectric Point ; Microvilli ; Nephritis ; Podocytes ; Polymers ; Proteinuria*

OBJECTIVETo analyze the clinical features and gene mutations of 6 Chinese children with Dent's disease.

METHODThe clinical and laboratory data of 6 children with Dent's disease were summarized. CLCN5 gene was analyzed using PCR amplification and DNA sequencing.

RESULTAll the six patients presented with low molecular weight proteinuria and hypercalciuria, including 3/6 hematuria, 4/6 nephrocalcinosis, 3/6 hypophosphatemia, 1/6 rickets. Six mutations of the CLCN5 gene were revealed, including L594fsX595, R637X, R467X, IVS4-2A > G, S244L and V505G. The mutation L594fsX595, IVS4-2A > G and V505G was never reported before.

CONCLUSIONLow molecular weight proteinuria and hypercalciuria were the main clinical features of the six Chinese boys with Dent's disease. Dent's disease could be associated with a Bartter-like syndrome, which make the gene diagnosis more important.

Adolescent ; Child ; Child, Preschool ; Chloride Channels ; genetics ; Dent Disease ; complications ; diagnosis ; genetics ; Humans ; Hypercalciuria ; diagnosis ; genetics ; Male ; Mutation ; Pedigree ; Proteinuria ; diagnosis ; etiology ; genetics

Chloride (Cl) channels are probably found in every cell, from bacteria to mammals. Cl channels are distributed both in the plasma membrane and in intracellular organelles. Three well established structural classes of plasma membrane chloride channels now exist: the ligand-gated chloride channels, the cAMP-stimulated cystic fibrosis transmembrane conductance regulator channel, and the voltage-gated (or swelling-activated) members of the ClC chloride channel family. They have diverse functions, ranging from regulation of cell volume to transepithelial transport, homeostasis, and stabilization of membrane potential, signal transduction and acidification of intracellular organelles. These different functions require the presence of many distinct Cl channels, which are differentially expressed and regulated by various stimuli. A combination of mutagenesis and biophysical analysis has been used to correlate their structure with function. Also their physiological roles are explained by genetic defects leading to various inherited disease and knock-out mouse models. Thus, the loss of Cl channels leads to an impairment of transepithelial transport in Bartter's syndrome, to increased excitability in congenital myotonia, and to reduced endosomal acidification and impaired endocytosis in Dent's disease. Three major structural classes of chloride channels are known to date, but there may be others not yet identified at the molecular level. This review focuses on voltage-gated members of the ClC chloride channel family and their physiological roles.
Animals ; Bacteria ; Bartter Syndrome ; Cell Membrane ; Cell Size ; Chloride Channels ; Cystic Fibrosis Transmembrane Conductance Regulator ; Dent Disease ; Endocytosis ; Homeostasis ; Humans ; Ion Channels ; Mammals ; Membrane Potentials ; Mice ; Mutagenesis ; Myotonia ; Organelles ; Signal Transduction

Animals ; Child ; Child, Preschool ; Chloride Channels ; genetics ; Dent Disease ; complications ; diagnosis ; genetics ; therapy ; Diuretics ; therapeutic use ; Humans ; Hydrochlorothiazide ; therapeutic use ; Hypercalciuria ; diagnosis ; genetics ; Mutation ; genetics ; Phosphoric Monoester Hydrolases ; genetics ; Proteinuria ; diagnosis ; etiology ; genetics

Child ; Codon, Nonsense ; genetics ; DNA Mutational Analysis ; DNA Primers ; genetics ; Dent Disease ; diagnosis ; genetics ; Exons ; genetics ; Humans ; Infant ; Male ; Mutation ; Oculocerebrorenal Syndrome ; diagnosis ; genetics ; Phosphoric Monoester Hydrolases ; genetics ; Polymerase Chain Reaction