Bladder Exstrophy-Epispadias Complex (BEEC) is a congenital anomaly of the urinary tract that occurs in 1 in 20,000 to 80,000 births 1. However, in families with a previous occurrence of BEEC, the incidence is 1 in 100 births 2, a significant increase over the population incidence, indicating a possible genetic factor. Analysis of array Comparative Genomic Hybridization (aCGH) results from a BEEC patient population revealed a patient with a microduplication encompassing the G Protein-Coupled Receptor kinase 4 (GRK4) gene. Copy number variations of GRK4 are rare in the general population, with a frequency of 0.162% (https://decipher.sanger.ac.uk). Also, we identified 10 patients with urological defects, mainly of the kidney and bladder, with CNVs containing GRK4. The low frequency CNVs containing GRK4 and their association with urological defects makes GRK4 a promising candidate for study. GRK4 is one of six members of a G protein-coupled receptor kinase family that desensitize activated, agonist bound G protein-coupled receptors (GPCR) through phosphorylation. GRK4 is known to phosphorylate the dopamine D1 receptor, which leads to a decrease in cellular levels of cyclic AMP (cAMP). Sequencing and analysis of patient DNA revealed four patients with potentially dangerous mutations in the GRK4 gene. The object of my research was to identify the effects of GRK4 mutations found in BEEC patients on protein function, by measuring cAMP levels of cells containing mutated GRK4 transcripts.

Role of GRK4 in bladder exstrophy-epispadias complex

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.