title: Mutation analysis of five candidate genes in Chinese patients with hypospadias.
abstract: Hypospadias is the displacement of the urethral meatus from the tip of the glans to the ventral side of the phallus. During fetal development, SRY, SOX9, WT1, SRD5A2 and AR are important at different stages in the differentiation and development of the male genital system. Mutations in these genes impair masculinization and may be associated with hypospadias. In order to explore these possibilities, we employed polymerase chain reaction and direct sequencing to analyze the coding regions of these five genes in 90 Chinese hypospadias patients. We found a total of 16 different mutations in SRD5A2, AR and WT1 in 24 of these 90 patients. Seven mutations are novel. No mutation was found in SRY or SOX9. SNP V89L found in SRD5A2 was statistically significant between patients and controls. Our results indicated that mutations in SRD5A2, AR and WT1 were associated with hypospadias. In conclusion, mutations are frequently found in genes that control androgen action and metabolism, but are seldom found in genes active in the early phase of sex determination and differentiation. Mutations in AR, SRD5A2 or WT1 seem to be associated not only with hypospadias but also with micropenis.
authors.affiliation: Institute of Basic Medical Sciences, PUMC&CAMS, Beijing, 100005, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Jiajie
authors.initials: J
authors.lastname: Xu
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Liu
authors.forename: Weiqiu
authors.initials: W
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Fen
authors.initials: F
authors.lastname: Ma
authors.forename: Taiji
authors.initials: T
authors.lastname: Chen
authors.forename: Senkai
authors.initials: S
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000293:Adolescent; D002648:Child; D002681:China; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics; D006609:High Mobility Group Proteins / Q000235:genetics; D006801:Humans; D007021:Hypospadias / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D011944:Receptors, Androgen / Q000235:genetics*; D055758:SOX9 Transcription Factor; D017422:Sequence Analysis, DNA; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: C410798:AR protein, human; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; D011944:Receptors, Androgen; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D025721:WT1 Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase