ABSENCE OF PAX2 GENE-MUTATIONS IN PATIENTS WITH PRIMARY FAMILIAL VESICOURETERAL REFLUX

Vesicoureteric reflux (VUR) is a common childhood condition characteri sed by regurgitation of urine fi am the bladder to the kidney. It is t he commonest cause of end stage renal failure in children and an impor tant cause in adults. Primary VUR is often familial, suggesting that g enetic factors play an important role in its aetiology, Recently, VUR was observed as part of a syndrome, involving optic nerve colobomas an d renal anomalies, caused by mutations of the PAX2 gene. PAX2 is a mem ber of the paired box family of genes and is expressed in the ureteric bud and differentiating nephrogenic mesenchyme of the developing kidn ey, PAX2 has been shown to play a critical role in the development of both the kidney and the meter The occurrence of VUR in one family with the PAX2 mutation, and the expression pattern of PAX2 in developing u reteric bud, strongly suggested that PAX2 could be the cause of primar y familial VUR. Single strand conformational polymorphism (SSCP) analy sis of 23 affected subjects in eight families with primary familial WR showed no alterations in exons 2-5 of the PAX2 gene, in addition, a p olymorphic dinucleotide repeat marker located within the PAX2 gene seg regated independently of the disease trait in one large family who pri marily had VUR or reflux nephropathy. These results suggest that PAX2 is not a major cause of primary familial reflux.