Bladder exstrophy-epispadias complex:: Investigation of suppressor of variegation, enhancer of zeste and Trithorax (SET) as a candidate gene in a large cohort of patients

Objective. The bladder exstrophy-epispadias complex (BEEC) describes a rare anterior midline defect with variable expression involving the infra-umbilical abdominal wall, including the pelvis, urinary tract and external genitalia. It is assumed that the underlying cause of BEEC is a multifactorial mode of inheritance; however, its aetiology remains unknown. Only a few BEEC patients with distinctive cytogenetic features such as numeric or structural chromosomal abnormalities have been reported. The observation of translocations concerning the region of chromosome 9q32-q34.1 in two patients implies that this region bears a candidate gene which, during early blastogenesis, governs the development of this primary field. In this context, we considered the suppressor of variegation, enhancer of zeste and Trithorax ( SET) gene, located at chromosome 9q34, to be a good candidate, as the protein encoded is involved in the regulation of cell proliferation and differentiation. Moreover, SET expression was detected in embryonic kidney. Material and methods. A total of 33 patients affected with BEEC were analysed for mutations in the SET gene. Results. SET analysis did not reveal either a mutation or the presence of four single-nucleotide polymorphisms (dbSNP124) already described in the database. Conclusions. The data obtained in this study most likely exclude the SET gene as a possible genetic cause of BEEC. Hence, other genes in this region may contribute to the development of this midline defect.