Congenital anomalies of the kidney and urinary tract (CRUTA) are a major cause of renal dysfunction in childhood and span a wide range of urinary system malformations including ureteropelvic junction (UPJ) obstruction; vesicoureteral reflux (VUR); hypoplastic or multicystic dysplastic kidneys; and bladder outlet obstruction. Many of these anomalies often coexist; ie renal hypoplasia/dysplasia with UPJ obstruction. Also, VUR can often be seen in the contralateral side of individuals with ureteral duplication, or renal dysplasia. There is now growing evidence that these different renal and urologic malformations may be caused by mutations in the same gene(s). Although the etiology of CRUTA is probably multifactorial, it is likely that many of the CRUTA cases have a genetic cause. In fact many of these malformations often show familial clustering with variable penetrance. Recent studies have identified mutations in several genes involved in the development of kidney (such as PAX2, GATA3, EYA, and WT-1) that have been associated with CRUTA in humans. Recently mice, especially males, with a disrupted angiotensin type 2 receptor gene, have been shown to have a range of CRUTA. Also, Caucasian males with CRUTA have been reported to have a mutation in intron 1 of this gene. All of these studies point to the genetic heterogeneity of CRUTA. In addition to CRUTA, another common kidney disease, i.e. nephrotic syndrome (NS) / focal segmental glomerulosclerosis (FSGS), is increasingly thought to have a genetic basis and several cases ofNS/FSGS with VUR have been reported. Also over the last five years several genes, including NPHS1 (nephrin), ACTN4, and NPHS2 (podocin), and chromosomal regions (i.e. 1lq22, 19q13) have been identified for their association with NS / FSGS. However none of these NS/FSGS genes are associated with CRUTA. Although cases of 13q deletion syndrome have been previously identified with renal malformations, its association with SRNS has not been previously reported and no information is available on the critical regions on 13q associated with renal development. We identified eight children with 13q deletion, who had a range of CRUTA, with one child having steroid resistant nephrotic syndrome (SRNS). We performed cytogenetic and molecular genetic studies to identify the region(s) on 13q associated with renal development and disease and recently identified two critical regions, with one region lying on 13q22 and the other on 13q32. We wish to pursue further gene localization studies on chromosome 13 in this application in order to identify the causative genes.
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