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[Molecular basis of vesicoureteral reflux]
1Dipartimento di Pediatria, Seconda Università degli Studi, Napoli, Italy. giuliana.lama@unina2.it
Insights
Primary vesico-ureteral reflux (VUR) is a common genetic disorder in children. Research suggests VUR is inherited, likely as an autosomal dominant condition, implicating genes in excretory system development.
Area of Science:
- Pediatric Urology
- Medical Genetics
- Embryology
Context:
- Primary vesico-ureteral reflux (VUR) affects 0.5-1% of children, with sibling incidence up to 45%.
- VUR stems from structural defects at the vesico-ureteral junction, potentially linked to abnormal ureteral bud development.
Purpose:
- To explore the genetic underpinnings of primary vesico-ureteral reflux (VUR).
- To investigate the role of genes, such as PAX2, in the embryogenesis of the excretory system and their association with VUR.
Summary:
- VUR etiology is poorly understood but linked to abnormal ureteral bud development and gene interactions.
- PAX2 gene mutations are associated with VUR in some syndromes, though not universally implicated in familial VUR.
- Evidence suggests VUR is a genetic condition, likely inherited in an autosomal dominant pattern.
Impact:
- Identifies specific genes as potential candidates for VUR.
- Provides insight into the complex molecular pathways governing excretory system embryogenesis.
- Establishes a genetic basis for VUR, guiding future research and diagnostic approaches.
Abstract:
Primary vesico-ureteral reflux (VUR) is a common disorder in children, with an incidence in an unselected population between 0.5-1%. Twenty seven to forty five percent of an affected patient's siblings will have VUR between birth and children of 2 years or younger. VUR is caused by a structural abnormality of the vesico-ureteral junction, characterised by an abnormally short submucosal segment of the ureter or deficiency in the musculature of the intravesical ureter. The etiology of this malformation is currently not well known, but it is probably related to an abnormal development of the ureteral bud. Several genes, such as PAX2 or similar genes, are involved in this development and the interrelationship between these different genes is slowly being unravelled, providing a first insight into the complex molecular cascade directing the embryogenesis of the excretory system. Each gene involved in the development of the excretory system is a potential candidate gene for VUR. Sanyanusin et al. have identified frameshift mutations in exon 5 in PAX2 in several patients with coloboma-ureteric-renal syndrome, which involved VUR as part of the phenotype. In a separate study, linkage to PAX2 was excluded in a three generation pedigree involving individuals with VUR and renal hypoplasia. These results suggest that VUR is a genetic condition, inherited as an autosomal dominant disorder.