Mutation Update of the CLCN5 Gene Responsible for Dent Disease 1

Mansour-Hendili, Lamisse; Blanchard, Anne; Le Pottier, Nelly; Roncelin, Isabelle; Lourdel, Stéphane; Treard, Cyrielle; González, Wendy; Vergara-Jaque, Ariela; Morin, Gilles; Colin, Estelle; Holder-Espinasse, Muriel; Bacchetta, Justine; Baudouin, Véronique; Benoit, Stéphane; Bérard, Etienne; Bourdat-Michel, Guylhène; Bouchireb, Karim; Burtey, Stéphane; Cailliez, Mathilde; Cardon, Gérard; ... (2015). Mutation Update of the CLCN5 Gene Responsible for Dent Disease 1. Human mutation, 36(8), pp. 743-752. Wiley-Blackwell 10.1002/humu.22804

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Dent disease is a rare X-linked tubulopathy characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis and/or nephrolithiasis, progressive renal failure, and variable manifestations of other proximal tubule dysfunctions. It often progresses over a few decades to chronic renal insufficiency, and therefore molecular characterization is important to allow appropriate genetic counseling. Two genetic subtypes have been described to date: Dent disease 1 is caused by mutations of the CLCN5 gene, coding for the chloride/proton exchanger ClC-5; and Dent disease 2 by mutations of the OCRL gene, coding for the inositol polyphosphate 5-phosphatase OCRL-1. Herein, we review previously reported mutations (n = 192) and their associated phenotype in 377 male patients with Dent disease 1 and describe phenotype and novel (n = 42) and recurrent mutations (n = 24) in a large cohort of 117 Dent disease 1 patients belonging to 90 families. The novel missense and in-frame mutations described were mapped onto a three-dimensional homology model of the ClC-5 protein. This analysis suggests that these mutations affect the dimerization process, helix stability, or transport. The phenotype of our cohort patients supports and extends the phenotype that has been reported in smaller studies.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > School of Dental Medicine > Department of Orthodontics
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Endokrinologie / Diabetologie / Metabolik (Pädiatrie)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Janner, Marco

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1059-7794

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

André Schaller

Date Deposited:

29 Mar 2016 14:38

Last Modified:

30 Mar 2016 20:01

Publisher DOI:

10.1002/humu.22804

PubMed ID:

25907713

Uncontrolled Keywords:

CLCN5; ClC-5; Dent disease 1; low molecular weight proteinuria; renal failure

BORIS DOI:

10.7892/boris.79369

URI:

https://boris.unibe.ch/id/eprint/79369

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