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J Pediatr Genet 2012; 01(01): 015-023
DOI: 10.3233/PGE-2012-005
Georg Thieme Verlag KG Stuttgart – New York

Novel OCRL mutations in patients with Dent-2 disease

Detlef Böckenhauer
a   Department of Nephrology, Great Ormond Hospital for Children, London, UK
,
Arend Bökenkamp
b   Department of Pediatric Nephrology, VU University Medical Center, Amsterdam, The Netherlands
,
Matti Nuutinen
c   Department of Pediatrics and Adolescence, Oulu University Hospital, Oulu, Finland
,
Robert Unwin
d   UCL Centre for Nephrology, Royal Free Hospital and Campus, University College Medical School, London, UK
,
William van't Hoff
a   Department of Nephrology, Great Ormond Hospital for Children, London, UK
,
Tony Sirimanna
e   Department of Audiology, Great Ormond Hospital for Children, London, UK
,
Kristina Vrljicak
f   Department of Nephrology, University Children' Hospital, Zagreb, Croatia
,
Michael Ludwig
g   Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany
› Author Affiliations
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Further Information

Publication History

21 October 2010

07 December 2010

Publication Date:
27 July 2015 (online)

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Abstract

Dent disease is an X-linked tubulopathy frequently caused by mutations in the CLCN5 gene encoding the voltage-gated chloride channel and chloride/proton antiporter, ClC-5. About 15% of patients with a Dent' phenotype have mutations in the OCRL gene, which also causes Lowe oculocerebrorenal syndrome. To distinguish these patients from the more severe Lowe phenotype, they are diagnosed as having Dent-2 disease. We studied 14 CLCN5-negative patients from 12 families with a phenotype resembling Dent disease for defects in OCRL. In six of these kindreds three novel (c.149+1G>A, c.1126A>T, c.1547T>C) and three repeatedly observed mutations (c.166_167delTT, c.901C>T, c.1426C>T) were discovered. With the exception of a lower prevalence of nephrocalcinosis, the renal phenotype is identical with patients harboring a CLCN5 mutation. Affected children may have some of the extra-renal symptoms of Lowe syndrome, such as peripheral cataracts, mental impairment, stunted growth or elevation of creatine kinase/lactate dehydrogenase, blurring the distinction between those two clinical entities.

Keywords

Dent-2 disease - OCRL gene - proximal tubulopathy - cataracts - mental retardation