SNOMEDCT: 717790004; ORPHA: 1652, 93623; DO: 0050699, 0081454;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xq26.1 | Dent disease 2 | 300555 | X-linked recessive | 3 | OCRL | 300535 |
A number sign (#) is used with this entry because of evidence that Dent disease-2 (DENT2) is caused by mutation in the OCRL gene (300535) on chromosome Xq26.
See also Lowe oculocerebrorenal syndrome (OCRL; 309000), an allelic disorder with a more severe phenotype including extrarenal manifestations.
Dent disease-2 (DENT2) is an X-linked disorder of renal tubular epithelial function in which all of the clinical findings may be traced to impaired reabsorption of filtered solutes. Characteristic abnormalities include low molecular weight proteinuria and other features of Fanconi syndrome (see 134600), such as glycosuria, aminoaciduria, and phosphaturia, but typically do not include proximal renal tubular acidosis. Progressive renal failure is common, as are nephrocalcinosis and kidney stones (summary by Hoopes et al., 2005).
For a discussion of genetic heterogeneity of Dent disease, see 300009.
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).
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.
Bockenhauer, D., Bokenkamp, A., Nuutinen, M., Unwin, R., van't Hoff, W., Sirimanna, T., Vrljicak, K., Ludwig, M. Novel OCRL mutations in patients with Dent-2 disease. J. Pediat. Genet. 1: 15-23, 2012. [PubMed: 27625797] [Full Text: https://doi.org/10.3233/PGE-2012-005]
Hoopes, R. R., Shrimpton, A. E., Knohl, S. J., Hueber, P., Hoppe, B., Matyus, J., Simckes, A., Tasic, V., Toenshoff, B., Suchy, S. F., Nussbaum, R. L., Scheinman, S. J. Dent disease with mutations in OCRL1. Am. J. Hum. Genet. 76: 260-267, 2005. Note: Erratum: Am. J. Hum. Genet. 81: 634 only, 2007. [PubMed: 15627218] [Full Text: https://doi.org/10.1086/427887]
Levin-Iaina, N., Dinour, D. Renal disease with OCRL1 mutations: Dent-2 or Lowe syndrome? (Editorial) J. Pediat. Genet. 1: 3-5, 2012. [PubMed: 27625794] [Full Text: https://doi.org/10.3233/PGE-2012-002]