A locus for renal malformations including vesico-ureteric reflux on chromosome 13q33-34

Congenital anomalies of kidney and urinary tract (CAKUT), including vesico-ureteric reflux (VUR), are major causes of ESRD in childhood. Herein is reported evidence for a locus on 13q33q34 associated with CAKUT. Deletion mapping of chromosome 13q was performed in four children with CAKUT using 31 microsatellite markers on peripheral blood genomic DNA that was obtained from the patients and their parents. mRNA expression of the positional candidate genes was compared with sequences in electronic databases in silico and also studied in adult and fetal mouse kidneys using reverse transcription-PCR. The children (three girls; age range 5 to 17 yr) had varying severity of developmental delay and other organ system involvement. The spectrum of CAKUT included high-grade VUR (n = 2), renal dysplasia (n = 2), and hydronephrosis (n = 1). Both the children with VUR had evidence of renal failure with one of them developing ESRD. Deletion mapping identified a 7-Mb critical region flanked by markers D13S1311 and D13S285. There are 33 genes (12 known; 21 computer predicted) in this region. In silico expression studies showed matches for 14 of these genes in the kidneys and 10 in the bladder expressed sequenced tags databases. Mouse kidney studies showed that of the 24 genes examined, several had variable expression through the different stages of renal development, whereas five of the genes were not expressed at all. Herein is reported a new locus on chromosome 13q33q34 that can be associated with VUR with several genes showing mRNA expression patterns that suggest their potential for involvement in renal/urinary tract developmental anomalies.