Format

Send to

Choose Destination
See comment in PubMed Commons below
Hum Genet. 2003 Nov;113(6):480-5. Epub 2003 Aug 29.

De novo insertion of an Alu sequence in the coding region of the CLCN5 gene results in Dent's disease.

Author information

1
Research Unit, Nuestra Señora de Candelaria University Hospital, Carretera del Rosario s/n, 38010 Santa Cruz de Tenerife, Spain. fclamar@gobiernodecanarias.org

Abstract

Dent's disease is an X-linked renal tubular disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and eventual renal failure. Various types of mutations in the renal chloride channel gene, CLCN5, have been identified in patients with this disease. We studied a Spanish patient with Dent's disease and found, by polymerase chain reaction amplification of the CLCN5 exons, an abnormally large exon 11. Sequencing analysis revealed that this was attributable to the insertion in codon 650 of an Alu element of the "young" Ya5 subfamily. The Alu element was inserted with the same orientation as the CLCN5 gene and arose de novo on the maternal chromosome. Polymorphism analysis indicated that the insertion occurred in the germline of the maternal grandfather. The presence of a long poly(A) tract and evidence for a 16-bp target-site duplication implied that the Alu element was integrated by retrotransposition. This mutation predicts a truncated ClC-5 protein that lacks part of the carboxy-terminus and is likely to result in loss of function of the chloride channel. Insertions of Alu sequences, which are rarely found in coding regions, have occasionally been reported to cause other genetic diseases. However, this is the first report of a retrotransposon insertion in the CLCN5 gene associated with Dent's disease.

PMID:
14569459
DOI:
10.1007/s00439-003-0991-8
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Springer
    Loading ...
    Support Center