尿道下裂的基因特点及其研究进展

尿道下裂是男性新生儿中常见的先天性泌尿系统畸形。主要是由阴茎和尿道发育异常引起的,是一种多因素疾病,个体差异明显。目前研究发现,多种因素均与尿道下裂有关,包括遗传因素、产前激素不足、母体胎盘因素及环境影响,因此,尿道下裂往往是多因素结合的产物。在过去的十年间,大量研究致力于揭示尿道下裂的遗传基因特点。这些研究包括骨形成蛋白(BMP)、成纤维细胞生长因子(FGF)、同源盒基因A(HOXA)等基因,涵盖了性别基因的转录、性激素的合成及相关基因的信号传导。尽管目前发现了大量尿道下裂相关基因,但仍需大样本病例临床对照研究明确这些基因的诊断效能及生物学意义。同时,随着测序技术的发展,外显子和全基因组测序也将揭示基因与基因、基因与环境的相互作用,更好地探索尿道下裂的分子机制,从而探寻合适分子标记物及治疗干预的靶点。综述这一领域的研究现状,并对一些与尿道下裂有关基因的研究进展进行探讨。

Genetic Factors and Hypospadias

Hypospadias, one of the most common congenital malformations in male neonates, is due to abnormal penis and urethral development. It is a highly heterogeneous disorder that is related to multiple factors including genetic factor, hormonal insufficient, maternal and placental factor and environment factor. During the last decade, a tremendous work has been devoted to the molecular genetics of isolated hypospadias including the study of BMP, FGF, HOXA and so on. The related genes covered gender, steroidogenesis and signaling genes. It is necessary to study the biological functions of those genes and potential application in diagnosis by the case-control study with large samples. With the development of sequencing technique, the interaction of gene-gene or gene-environment will be decoded through new exome sequencing and whole genome sequencing, which is helpful for us to understand better the molecular mechanism of hypospadias and to explore the diagnosis markers and therapy targets. In this paper, we review the genetic factors of hypospadias and the research progress.