Dent disease is a rare X-linked recessive inherited renal tubular disorder characterized by low molecular weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, and other clinical features, and can lead to progressive renal failure. It is primarily caused by mutations in the CLCN5 gene. This article reports the case of a 10-year-old male patient of Chinese descent who was incidentally found to have asymptomatic proteinuria during a routine health examination. Comprehensive biochemical testing and clinical evaluation revealed significant LMWP and hypercalciuria, while renal biopsy showed mesangial cell and matrix proliferation. Whole exome sequencing identified a novel deletion mutation in the CLCN5 gene (NM_001127899.4, c.1158delC, p.F387Lfs*42) causing a frameshift and premature termination, which is likely to disrupt its role in chloride/hydrogen ion exchange and endosomal acidification. Bioinformatic analysis indicated the variant is pathogenic. Genetic testing plays an important role in diagnosing rare kidney diseases. Early identification of pathogenic mutations is essential for facilitating timely intervention and appropriate management, potentially enhancing patient outcomes. This report expands the CLCN5 mutation spectrum and contributes to understanding the genetic and molecular mechanisms of Dent disease.
Humans ; Chloride Channels/genetics* ; Dent Disease/genetics* ; Male ; Child ; Computational Biology ; Mutation ; Proteinuria/genetics* ; Hypercalciuria/genetics*

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

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

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