CLCN5 chloride-channel mutations in six new North American families with X-linked nephrolithiasis. Kidney Int 1998 Sep;54(3):698-705
Date
09/12/1998Pubmed ID
9734595DOI
10.1046/j.1523-1755.1998.00061.xScopus ID
2-s2.0-0031708210 (requires institutional sign-in at Scopus site) 57 CitationsAbstract
BACKGROUND: X-linked nephrolithiasis, or Dent's disease, encompasses several clinical syndromes of low molecular weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and renal failure, and is associated with mutations in the CLCN5 gene encoding a kidney-specific voltage-gated chloride channel. Some patients from Europe have rickets, and all symptomatic patients confirmed by mutation analysis have been male.
METHODS: We analyzed the CLCN5 DNA sequence in six new families with this disease.
RESULTS: In three probands, a single-base substitution yielded a nonsense triplet at codons 28, 34, and 343, respectively, and in two families, one of which was Hispanic, we found single-base deletions at codons 40 and 44, leading to premature termination of translation. In the sixth family, a single-base change from C to T predicted substitution of leucine for serine at codon 244, previously reported in two European families with prominent rickets, though this patient of Ashkenazi origin did not have rickets. Each of these mutations was confirmed by restriction endonuclease analysis, or repeat sequencing and CFLP. The R34X mutation occurred in a Canadian infant with severe rickets. The family with the R28X nonsense mutation included one woman with recurrent kidney stones and another woman with glomerular sclerosis. In another family, a woman heterozygous for the W343X mutation also had nephrolithiasis.
CONCLUSIONS: These studies expand the range of mutations identified in this disease, and broaden the phenotypic range to include clinically affected women and the first North American case with severe rickets.
Author List
Hoopes RR Jr, Hueber PA, Reid RJ Jr, Braden GL, Goodyer PR, Melnyk AR, Midgley JP, Moel DI, Neu AM, VanWhy SK, Scheinman SJAuthor
Scott K. Van Why MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Aged, 80 and over
Amino Acid Sequence
Child
Chloride Channels
Female
Genetic Linkage
Humans
Kidney Calculi
Male
Middle Aged
Molecular Sequence Data
Mutation
X Chromosome
