ORPHA: 289365; DO: 9620;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3p12.3 | Vesicoureteral reflux 2 | 610878 | Autosomal dominant | 3 | ROBO2 | 602431 |
A number sign (#) is used with this entry because of evidence that vesicoureteral reflux-2 (VUR2) is caused by heterozygous mutation in the ROBO2 gene (602431) on chromosome 3p12.
For a phenotypic description and a discussion of genetic heterogeneity of vesicoureteral reflux, see 193000.
Lu et al. (2007) described 2 families in which autosomal dominant inheritance of vesicoureteral reflux (VUR) was associated with mutation in the ROBO2 gene. The first was a Caucasian British family in which the affected daughter had bilateral VUR, hypoplastic kidneys, and nephropathy. Her mother required ureteral reimplantation because of severe VUR. The second was a Caucasian Dutch family in which the proband had bilateral VUR and a right duplex collection system and kidney. Her mother and 2 aunts had urinary tract symptoms and ultrasonographic evidence of congenital anomalies of the kidney and urinary tract (CAKUT), whereas her grandmother had a unilateral small kidney.
Lu et al. (2007) investigated a man with a de novo translocation, 46,X,t(Y;3);(p11;p12)dn, who exhibited multiple congenital abnormalities, including severe bilateral VUR with ureterovesical junction defects. This translocation disrupted ROBO2 (602431), which encodes a transmembrane receptor for SLIT ligand (see SLIT2; 603746), and produced dominant-negative ROBO2 proteins that abrogated SLIT-ROBO signaling in vitro. In addition, Lu et al. (2007) identified 2 novel ROBO2 intracellular missense variants (602431.0001, 602431.0002) that segregated with congenital anomalies of the kidney and urinary tract (CAKUT) and VUR in 2 unrelated families. Adult heterozygous and mosaic mutant mice with reduced Robo2 gene dosage also exhibited striking CAKUT-VUR phenotypes. Collectively, these results implicated the SLIT-ROBO signaling pathway in the pathogenesis of a subset of human VUR.
Lu, W., van Eerde, A. M., Fan, X., Quintero-Rivera, F., Kulkarni, S., Ferguson, H., Kim, H.-G., Fan, Y., Xi, Q., Li, Q., Sanlaville, D., Andrews, W., and 15 others. Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux. Am. J. Hum. Genet. 80: 616-632, 2007. [PubMed: 17357069] [Full Text: https://doi.org/10.1086/512735]