ROLE OF HPS.E2 IN UROFACIAL SYNDROME AND OTHER NON-NEUROGENIC VOIDING DYSFUNCTIONS

Abstract

Voiding dysfunctions account for 40% of pediatrics urological visits. They occur due to neurological problems where the nerve supply to the bladder is interrupted, or non-neurological problems where nerves are intact though the child is experiencing symptoms of neurological forms. Some genetic diseases cause dysfunctional voiding in children known as Urofacial syndrome (UFS). Although UFS is rarely reported in the medical literature, it might be underd.iagnosed either due to physicians' lack of knowledge or because it is presented in a dose-dependent manner. UFS is caused by mutation in HPSE2 gene, which encodes for heparanase-2 protein. 1-1.eparanase-2 function is not well understood, and studies of its role in voiding dysfunction are ongoing. Since .UFS shares symptoms similar to those of other voiding dysfunctions, it can be a useful model to study the pathoetiology of voiding disorders, because it is caused by dysfunction of protein that might have roles in other voiding problems. This project aims to link the genotype of heparanase-2 with the phenotype in children with non neurological voiding dysfunction by testing them for the presence of dysfunctional heparanase-2. Identification of the heparanase-2 function in the bladder organogenesis will be based on a mouse-knockout model using morpholinos (class of antisense) to ablate heparanase-2 function.