Locus heterogeneity of Dent's disease: OCRL1 and TMEM27 genes in patients with no CLCN5 mutations.

Full Abstract

Dent's disease is an X-linked renal tubulopathy caused by mutations mainly affecting the CLCN5 gene. Defects in the OCRL1 gene, which is usually mutated in patients with Lowe syndrome, have recently been shown to lead to a Dent-like phenotype, called Dent's disease 2. About 25% of Dent's disease patients do not carry CLCN5/OCRL1 mutations. The CLCN4 and SLC9A6 genes have been investigated, but no mutations have been identified. The recent discovery of a novel mediator of renal amino acid transport, collectrin (the TMEM27 gene), may provide new insight on the pathogenesis of Dent's disease. We studied 31 patients showing a phenotype resembling Dent's disease but lacking any CLCN5 mutations by direct sequencing of the OCRL1 and TMEM27 genes. Five novel mutations, L88X, P161HfsX167, F270S, D506N and E720D, in the OCRL1 gene, which have not previously been reported in patients with Dent's or Lowe disease, were identified among 11 patients with the classical Dent's disease phenotype. No TMEM27 gene mutations were discovered among 26 patients, 20 of whom had an incomplete Dent's disease phenotype. Our findings confirm that OCRL1 is involved in the functional defects characteristic of Dent's disease and suggest that patients carrying missense mutations in exons where many Lowe mutations are mapped may represent a phenotypic variant of Lowe syndrome.

Author information

Author/s: Tosetto, Enrica (E); Addis, Maria (M); Caridi, Gianluca (G); Meloni, Cristiana (C); Emma, Francesco (F); Vergine, Gianluca (G); Stringini, Gilda (G); Papalia, Teresa (T); Barbano, Giancarlo (G); Ghiggeri, Gian Marco (GM); Ruggeri, Laura (L); Miglietti, Nunzia (N); D Angelo, Angela (A); Melis, Maria Antonietta (MA); Anglani, Franca (F);

Affiliation: Division of Nephrology, Department of Medical and Surgical Sciences, University of Padua, 35128 Padova, Italy.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Pediatric nephrology (Berlin, Germany) (Pediatr Nephrol), published in Germany. (Language: eng)

Reference: 2009-Oct; vol 24 (issue 10) : pp 1967-73

Dates: Created 2009/08/25; Completed 2009/11/17;

PMID: 19582483, status: MEDLINE (last retrieved date: 11/17/2009)

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Chloride Channels - genetics
DNA Mutational Analysis
Genetic Diseases, X-Linked - genetics
Humans
Kidney Diseases - genetics
Male

Membrane Glycoproteins - genetics
Mutation
Oculocerebrorenal Syndrome - genetics
Phenotype
Phosphoric Monoester Hydrolases - genetics
Polymerase Chain Reaction

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: CLC-5 chloride channel (0) ; Chloride Channels (0) ; Membrane Glycoproteins (0) ; TMEM27 protein, human (0) ; Phosphoric Monoester Hydrolases (EC 3.1.3.-) ; OCRL protein, human (EC 3.1.3.36)

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