A common molecular basis for three inherited kidney stone diseases
| Autor: | Simon E. Fisher, Steven J. Scheinman, Blanche Schwappach, Sarah E. Lloyd, Alessandra Bolino, Paul Goodyer, Marcella Devoto, Simon H. S. Pearce, Thomas J. Jentsch, Brian Harding, Ian W. Craig, Oliver Wrong, S.P.A. Rigden, Rajesh V. Thakker, Klaus Steinmeyer |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
medicine.medical_specialty Candidate gene Protein Conformation Xenopus DNA Mutational Analysis Molecular Sequence Data Dent Disease Polymerase Chain Reaction Kidney Calculi Chloride Channels Internal medicine Electrochemistry medicine Animals Missense mutation Hypercalciuria Amino Acid Sequence Cells Cultured Genetics Kidney Multidisciplinary Dent's disease Base Sequence biology CLCN5 DNA medicine.disease Recombinant Proteins Pedigree medicine.anatomical_structure Endocrinology Mutation biology.protein Calcium Female Kidney stones |
| Popis: | Kidney stones (nephrolithiasis), which affect 12% of males and 5% of females in the western world, are familial in 45% of patients and are most commonly associated with hypercalciuria. Three disorders of hypercalciuric nephrolithiasis (Dent's disease, X-linked recessive nephrolithiasis (XRN), and X-linked recessive hypophosphataemic rickets (XLRH)) have been mapped to Xp11.22 (refs 5-7). A microdeletion in one Dent's disease kindred allowed the identification of a candidate gene, CLCN5 (refs 8,9) which encodes a putative renal chloride channel. Here we report the investigation of 11 kindreds with these renal tubular disorders for CLCN5 abnormalities; this identified three nonsense, four missense and two donor splice site mutations, together with one intragenic deletion and one microdeletion encompassing the entire gene. Heterologous expression of wild-type CLCN5 in Xenopus oocytes yielded outwardly rectifying chloride currents, which were either abolished or markedly reduced by the mutations. The common aetiology for Dent's disease, XRN and XLRH indicates that CLCN5 may be involved in other renal tubular disorders associated with kidney stones. |
| Databáze: | OpenAIRE |
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