Dent Disease 2

A number sign (#) is used with this entry because Dent disease-2 is caused by mutation in the OCRL gene (300535) on chromosome Xq26.

For a phenotypic description and a discussion of genetic heterogeneity of Dent disease, see 300009.

See also Lowe oculocerebrorenal syndrome (OCRL; 309000), an allelic disorder with a more severe phenotype including extrarenal manifestations.

Clinical Features

Hoopes et al. (2005) reported 5 families with Dent disease with mutations in the OCRL1 gene. PIP(2) 5-phosphatase activity was markedly reduced in skin fibroblasts cultured from the probands, and protein expression, measured by Western blot analysis, was reduced or absent. Slit-lamp examinations performed in childhood or adulthood for all 5 probands showed normal results. None of these patients had metabolic acidosis. Three of the 5 probands had mild mental retardation, whereas 2 had no developmental delay or behavioral disturbance.

Bockenhauer et al. (2012) reported 8 boys from 6 families with Dent disease-2. All had low molecular weight proteinuria and hypercalciuria, but none had renal tubular acidosis. About half had nephrocalcinosis. Two of the 8 patients had impaired cognitive function, 1 of whom also had early ocular nuclear densities. Other more variable extrarenal features among the patients included increased lactate dehydrogenase, increased creatine kinase, short stature, and umbilical hernia, some of which were reminiscent of Lowe syndrome. Bockenhauer et al. (2012) concluded that there is a broad phenotypic spectrum of OCRL mutations, suggesting that Dent disease-2 may be a mild variant of Lowe syndrome (Levin-Iaina and Dinour, 2012).

Molecular Genetics

Hoopes et al. (2005) reported affected members of 13 families with Dent disease in whom mutations in the CLCN5 gene (300008) were excluded, indicating genetic heterogeneity. In 5 of these 13 families, they identified mutations in the OCRL gene (see, e.g., 300535.0005 and 300535.0006).

Bockenhauer et al. (2012) identified 6 different mutations in the OCRL gene (see, e.g., 300535.0006-300535.0009) in 8 boys from 6 of 12 families with a phenotype resembling Dent disease who did not have mutations in the CLCN5 gene. Combined with other reports, the authors stated that OCRL mutations had been found in 43 (59.7%) of 72 families with a Dent disease phenotype.