Hiort O, Klauber G, Cendron M, Sinnecker G H, Keim L, Schwinger E, Wolfe H J, Yandell D W
Klinik für Pädiatrie, Medizinische Universität Lübeck, Germany.
Eur J Pediatr. 1994 May;153(5):317-21. doi: 10.1007/BF01956409.
Development of male external genitalia is dependent on androgens, and karyotypic males lacking appropriate levels of androgens or functionally normal receptors may show abnormal virilization. Mutations in the androgen receptor gene cause abnormal receptor function and diverse mutations may be associated with heterogeneous clinical signs of androgen insensitivity. In this study, we have searched for the existence of androgen receptor gene mutations carried by some patients with hypospadias. Genomic DNA samples from peripheral blood leucocytes from 21 patients with different degrees of hypospadias were studied. Analysis of the androgen receptor gene was performed by exon-specific amplification using polymerase chain reaction, single strand conformation polymorphism analysis, and direct genomic sequencing. Although a silent polymorphism was identified in exon 1 of the androgen receptor gene, the majority of patients studied (20/21) did not carry androgen receptor gene mutations. One patient with severe hypospadias and bilateral cryptorchidism was found to carry a point mutation in exon 8. We conclude that mutations in the androgen receptor gene may be carried by subset of patients with genital ambiguity presenting primarily with hypospadias, but this is not the underlying cause in the majority of cases. Characterization of this genetic defect may be important for classification and subsequent conservative therapeutic approaches for these patients.
男性外生殖器的发育依赖于雄激素，而缺乏适当水平雄激素或功能正常受体的核型男性可能会出现异常的男性化。雄激素受体基因突变会导致受体功能异常，多种突变可能与雄激素不敏感的异质性临床体征相关。在本研究中，我们探寻了一些尿道下裂患者是否携带雄激素受体基因突变。对21例不同程度尿道下裂患者外周血白细胞的基因组DNA样本进行了研究。采用聚合酶链反应进行外显子特异性扩增、单链构象多态性分析及直接基因组测序，对雄激素受体基因进行分析。虽然在雄激素受体基因外显子1中鉴定出一个沉默多态性，但大多数研究患者（20/21）未携带雄激素受体基因突变。发现1例重度尿道下裂伴双侧隐睾患者在外显子8中携带一个点突变。我们得出结论，雄激素受体基因突变可能存在于主要表现为尿道下裂的生殖器模糊患者亚组中，但在大多数情况下并非根本原因。对这种基因缺陷的特征描述对于这些患者的分类及后续保守治疗方法可能很重要。
