Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

The annual urinary screening of Japanese children above 3 yr of age has identified a progressive proximal renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria, and nephrocalcinosis. The disorder, which has a familial predisposition and occurs predominantly in males, has similarities to three X-linked proximal renal tubular disorders that are due to mutations in the renal chloride channel gene, CLCN5. We have investigated four unrelated Japanese kindreds with this tubulopathy and have identified four different CLCN5 mutations (two nonsense, one missense, and one frameshift). These are predicted to lead to a loss of chloride channel function, and heterologous expression of the missense CLCN5 mutation in Xenopus oocytes demonstrated a 70% reduction in channel activity when compared with the wild-type. In addition, single-stranded conformation polymorphism (SSCP) analysis was found to be a sensitive and specific mutational screening method that detected > 75% of CLCN5 mutations. Thus, the results of our study expand the spectrum of clinical phenotypes associated with CLCN5 mutations to include this proximal renal tubular disorder of Japanese children. In addition, the mutational screening of CLCN5 by SSCP will help to supplement the clinical evaluation of the annual urinary screening program for this disorder.

Original publication




Journal article


J Clin Invest

Publication Date





967 - 974


Adolescent, Adult, Amino Acid Sequence, Animals, Child, Child, Preschool, Chloride Channels, Chromosome Mapping, Codon, Nonsense, DNA Primers, Electrophoresis, Polyacrylamide Gel, Exons, Female, Frameshift Mutation, Gene Expression Regulation, Humans, Japan, Kidney Diseases, Male, Middle Aged, Molecular Sequence Data, Mutation, Nephrocalcinosis, Pedigree, Polymerase Chain Reaction, Polymorphism, Single-Stranded Conformational, Proteinuria, Renal Tubular Transport, Inborn Errors, Sequence Analysis, DNA, Sex, Xenopus