Gimelli et al. (2010) reported 2 unrelated families with vesicoureteral reflux associated in some cases with renal scarring and/or congenital anomalies of the kidney and urinary tract (CAKUT). In the first family, the young female proband had congenital ... Gimelli et al. (2010) reported 2 unrelated families with vesicoureteral reflux associated in some cases with renal scarring and/or congenital anomalies of the kidney and urinary tract (CAKUT). In the first family, the young female proband had congenital defects of the urinary tract, chronic constipation, and mild mental retardation, and she was conceived by in vitro fertilization. At 34 weeks' gestation, she had polyhydramnios and severe bilateral hydronephrosis necessitating cesarean section. Early in life, her right kidney showed a duplicated pyeloureteral collecting system about 7 cm in diameter, and bilateral VUR (grade III). Ureteroplasty was performed to correct these urinary defects. Other features of the patient included mild axial hypotonia, delayed psychomotor development with a defect in expressive language, a large patent ductus arteriosus, and thinning of the corpus callosum. The patient's mother showed grade IV VUR associated with megaureter, recurrent urinary infections, chronic constipation, and coloboma of the iris in her left eye. Cytogenetic analysis of the girl showed a de novo pseudodicentric duplication of chromosome 8q11-q12 of maternal origin. In the second family, a young male proband had left hydronephrosis due to stenosis of the pyeloureteral joint and grade III VUR; his mother also had grade III VUR. Four additional unrelated patients with sporadic occurrence of vesicoureteral reflux were also reported.
By candidate gene sequencing of a duplicated region of chromosome 8q11-q12 in a female patient with VUR, Gimelli et al. (2010) identified a heterozygous mutation in the SOX17 gene (Y259N; 610928.0001). The same heterozygous mutation was found in ... By candidate gene sequencing of a duplicated region of chromosome 8q11-q12 in a female patient with VUR, Gimelli et al. (2010) identified a heterozygous mutation in the SOX17 gene (Y259N; 610928.0001). The same heterozygous mutation was found in her affected mother, in an affected mother and son from an unrelated family, and in 2 of 178 patients with sporadic occurrence of VUR. Two additional patients with sporadic VUR were found to carry 2 different heterozygous mutations in the SOX17 gene (610928.0002 and 610928.0003, respectively). Gimelli et al. (2010) postulated that altered levels of WNT (see 164820) signaling during development caused the observed congenital urinary defects, although a role for alterations in other genes regulated by SOX17 could not be excluded.