Mutation analysis of five candidate genes in Chinese patients with hypospadias
Mutation analysis of five candidate genes in Chinese patients with hypospadias
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DOI：
10.1038/sj.ejhg.5201232
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发表时间：
2004-09-01
影响因子：
5.2
通讯作者：
Shen, Y
中科院分区：
文献类型：
--
作者：
Wang, YP;Li, Q;Shen, Y
尿道下裂是指尿道口从龟头的顶端移位到阴茎的腹侧。在胎儿发育过程中，SRY、SOX 9、WT 1、SRD 5A2和AR在男性生殖系统分化和发育的不同阶段都很重要。这些基因的突变损害男性化，可能与尿道下裂有关。为了探索这些可能性，我们采用聚合酶链反应和直接测序技术分析了90例中国尿道下裂患者这五个基因的编码区。我们在这90例患者中的24例中发现了SRD5A2、AR和WT1共16种不同的突变。七个突变是新的。未发现SRY和SOX 9突变。SRD5A2中V89L单核苷酸多态性在两组间差异有统计学意义。我们的结果表明SRD 5A2、AR和WT 1的突变与尿道下裂相关。总之，突变经常被发现在控制雄激素的作用和代谢的基因，但很少被发现在性别决定和分化的早期阶段的基因活跃。AR、SRD 5A2或WT 1的突变似乎不仅与尿道下裂有关，而且与小阴茎有关。
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.