Characterization of KCTD13 and CUL3: The Role of Ubiquitin Conjugating Complexes in the Development Hypospadias and Cryptorchidism

Congenital genitourinary systems are relatively common. These are cryptorchidism and hypospadias. Cryptorchidism is the failure of testis descent into the scrotum. It occurs in 6% of full-term newborn boys and by age one, the incidence declines to about 3%. Hypospadias is a midline fusion defect of the male ventral urethra and occurs in nearly 1 in 125 live male births. The etiology of these congenital GU birth defects is likely involves genetic, hormonal and environmental factors. Submicroscopic segmental variations in the genomes of unrelated subjects with hypospadias and cryptorchidism affect the core component of an E3 ubiquitin ligase complex, (cullin 3; CUL3) and one of its substrate recognition proteins (potassium channel tetramerisation domain containing 13; KCTD13). Currently, 29% (4/14) of subjects with hypospadias and cryptorchidism have segmental duplication or deletions that affect genes involved in ubiquitin-conjugation of target proteins. To better understand the importance of these genes in the development of hypospadias and cryptorchidism, we are looking for base-pair variations in the coding regions of CUL3 and KCTD13. Genomic DNA from subjects with no observed segmental variations affecting CUL3 and KCTD13 was used in this study. We hypothesize that, clinically significant (SNPs) are present in the coding region of KCTD13 and CUL3 in patients with hypospadias and cryptorchidism. Sequencing of patient exons 7, 8, 14, and 15 from CUL3 has not revealed nucleotide polymorphisms. Exon 15 may contain polymorphism resulting in an amino acid functional group change. We are confirming this data by sequencing the minus strand.