Absence of PAX2 gene mutations in patients with primary familial vesicoureteric reflux.

Abstract

Vesicoureteric reflux (VUR) is a common childhood condition characterised by regurgitation of urine from the bladder to the kidney. It is the commonest cause of end stage renal failure in children and an important cause in adults. Primary VUR is often familial, suggesting that genetic factors play an important role in its aetiology. Recently, VUR was observed as part of a syndrome, involving optic nerve colobomas and renal anomalies, caused by mutations of the PAX2 gene. PAX2 is a member of the paired box family of genes and is expressed in the ureteric bud and differentiating nephrogenic mesenchyme of the developing kidney. PAX2 has been shown to play a critical role in the development of both the kidney and the ureter. The occurrence of VUR in one family with the PAX2 mutation, and the expression pattern of PAX2 in developing ureteric bud, strongly suggested that PAX2 could be the cause of primary familial VUR. Single strand conformational polymorphism (SSCP) analysis of 23 affected subjects in eight families with primary familial VUR showed no alterations in exons 2-5 of the PAX2 gene. In addition, a polymorphic dinucleotide repeat marker located within the PAX2 gene segregated independently of the disease trait in one large family who primarily had VUR or reflux nephropathy. These results suggest that PAX2 is not a major cause of primary familial reflux.

Vesico-ureteric reflux and urinary tract development in thePax21Neu+/−mouse

“…Thus far, RCS-causing mutations have all been identified at the 5Ј-end of the PAX2 gene. Although one family study failed to identify PAX2 mutations in primary VUR (11), it is possible that mutations or polymorphisms at the 3Ј-end that affect the transactivation potential of PAX2 are associated with this condition (38,47).…”

A genome-wide scan for genes involved in primary vesicoureteric reflux

“…Linkage11 and mutation screening studies12 of UPK3A and other members of the uroplakin family13 14 (Kelly et al , unpublished data) in humans did not show evidence for their involvement in VUR, but mutations in UPK3A have now been found in some cases of renal aplasia, hypoplasia and dysplasia, including some with VUR 15 16. The PAX2 gene has been shown to be mutated in renal-coloboma syndrome, which includes VUR as part of a complex phenotype,17 18 and in renal hypoplasia and VUR without eye defects,19 but has not been found to be mutated in uncomplicated VUR 20. Investigation of a patient with multiple congenital anomalies, including severe bilateral VUR, found a Y;3 translocation that disrupted ROBO2 , and investigation of this gene in 124 families with VUR with potential autosomal dominance revealed mutations in two families 21.…”

Vesicoureteric reflux and renal malformations: a developmental problem

“…Although these syndromes and chromosomal abnormalities are rare, the associated genes have emerged as candidates for mutational analysis. To date, mutations in PAX2 have not been identified in patients with primary VUR (70).…”