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 ... 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 ... 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.