Novel OCRL mutations in patients with Dent-2 disease

• Published in: Journal of pediatric genetics (Birmingham, Ala.) Ala.), 2012-03, Vol.1 (1), p.015-023
• Main Authors: Böckenhauer, Detlef, Bökenkamp, Arend, Nuutinen, Matti, Unwin, Robert, van't Hoff, William, Sirimanna, Tony, Vrljicak, Kristina, Ludwig, Michael
• Format: Article
• Language: English
• Subjects: Calcinosis; Cataracts; Children; Chloride channels; CLCN5 gene; Creatine kinase; Kidney; Kidney diseases; L-Lactate dehydrogenase; Mutation; Protons; X chromosome
• ISSN: 2146-4596; 2146-460X
• DOI: 10.3233/PGE-2012-005

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.