Hypospadias Incidence Related Gene Mutation Research And The Prepuce Full Thickness Skin Graft (scrotal Skin Graft) Graft Coupled Preputial Island Flap In The Treatment Of Various Types Of Urethral Hypospadias

Hypospadias, one of the most common congenital anomalies of male urogenital system, is a disease in sexual mal-differentiation, and its etiology is unclear. The incidence of hypospadias is 3‰ and the incidence is increasing in many countries.The etiology of hypospaias is still unclear, although great progress has been made. At present, there are four factors that maybe affect the onset of hypospadias, including genetic factor, endocrine, environment and others.Normal sex differentiation of male is a consecutive, ordered and inter-related process, requiring equilibrium of many gene interactions. SRY gene is the initial point of male sex differentiation. SRY gene initiates a series of molecular cascade reaction which is very important for normal sex development. S0X9 and WTl are important genes in the anterior differentiation phase besides SRY. S0X9 is a downstream gene of SRY and plays pivot roles. Dihydrotestosterone is the key hormone responsible for the development of the male external genitalia, urethra and prostate. Dihydrotestosterone is derived from testosterone by catalysis of 5 α -steroid reductase, which is encoded by the gene SRD5A2. Testosterone and dihydrotestosterone can only be effective through binding to the androgen receptor encoded by gene AR. WT1 not only regulates cascade reaction of sex differentiation through interacting with SRY, MIS, SF1 and DAX1 but also participates i n the posterior developmental phase. MID1 is essential for the development of midline structure. SRY, WTl, S0X9, SRD5A2 AR and MID1 are all important in differentiation and development of male genital system and act in different stages. Therefore, the six genes were selected as first choice for hypospadias genetic analysis.All exons of above six genes were amplified from the genomic DNA of 95 cases. It is the first t ime t hat t he s erial genes w hich are related t o h ypospadias a re detected i n s o many patients. Mutations were detected by directly sequencing of PCR products. SRY gene was tested using multiplex PCR.18 mutations were detected from 24 cases, and the karyotypes were abnormal in 6 cases. The cases for these two types accounted for 31.6% of all cases. 10 mutations are novel. While in contol group, 2 mutations were detected from 5 cases. The difference is significant b etween c ontrol group and test group. The results of tested six genes are as follows. (1) SRY: no mutation was detected. SRY was negative in 4 cases, within which 3...