Background: Congenital anomalies of the kidneys and urinary tract (CAKUT) are frequently associated with malformations of other organs.
Methods: In order to explore the role of DNA microimbalances in syndromal CAKUT, we applied genome-wide array-based comparative genomic hybridization (array-CGH) in 30 children with various CAKUT phenotypes and at least one additional extrarenal symptom.
Results: In three patients, causal imbalances were detected: In one patient with duplex kidney and vesico-ureteral reflux associated with extrarenal stigmata, a terminal 9.52 Mb gain in chromosomal band 2q37.1-q37.3 and a terminal 5.65 Mb loss in 7q36.2-q36.3 were detected, which were due to an unbalanced 2;7-translocation according to FISH analysis. A balanced 2;7-translocation was present in the unaffected mother. In another patient presenting with renal hypoplasia and proximal ureteric stenosis combined with mental retardation, macrocephaly and ear anomalies, a duplication of 2.73 Mb was detected in 1q21.1. The unaffected father had a 1.3 Mb gain in 1q21.1-q21.2 involving the distal part of the patient's gain, for which benign copy number variation was described. A third patient affected by dysplastic kidney with a strongly dilated ureter and extrarenal abnormalities exhibited a de novo loss of 13.38 Mb in 3q23-q25.1 including the AGTR1 gene. However, no AGTR1 mutations were identified in the remaining allele of this case or in 108 patients with isolated renal dysplasia/hypoplasia.
Conclusions: In this study, 10% of patients with syndromic CAKUT were shown to carry DNA microimbalances, and four chromosomal regions presumably associated with the CAKUT phenotype were identified: 1q21.1, 2q37.1-q37.3, 3q23-q25.1 and 7q36.2-q36.3.