Study On The Steroidogenic Factor-1and The46,XY Hypospadias Including Cryptorchidism

Objective：To research the mutation of steroidogenic factor-1(SF-1)gene from46,XY hypospadias including cryptorchidism and therelationship between genotypes and phenotypes, then reveal the action ofSF-1in human gonadal differentiation and development.Methods：In the Children’s Hospitalof Chongqing MedicalUniversityof China, sixty46, XY hypospadias including cryptorchidism subjectswithout adrenal insufficiency and forty healthy male children with normalgenital development for control were collected. Genomic DNA wasextracted from fresh peripheral whole blood. The exons2-7andexon-intron boundaries of SF-1gene were amplified by polymerase chainreaction(PCR). The PCR products were directly sequenced, then for DNAsequence alignment using Standard Nuclear BLAST. The abnormal resultswere sepuenced for three times, and further confirmed by T-A cloning.Results: In our study, we detected a heterozygous deletion of SF-1gene from17hypospadias with cryptorchidism (1/17=4.9%). The patientwas diagnosed with female genitalia at birth and perineal hypospadias withbilateral cryptorchidism, sever underandrogenization. This mutationreplaced proline(P/Pro) at position125by a arginine(R/Arg), caused aframeshift, and prematurely terminated translation at position295(p.P125RfsX170). We alse found one single nucleotide polymorphism(SNP) rs1110061(G/C) of SF-1gene. No significantstatistical differences were found of the allele of G/C and genotype(GG/GC/CC) frequencies between the46, XY hypospadias includingcryptorchidism patients and controls.Conclusion: SF-1gene plays an important role in the early humangonadal differentiation and development. SF-1gene mutation was onepossible cause of46,XY hypospadias including cryptorchidism, itsphenotype is sever testicular dysgensis including severunderandrogenization.