Patterson M N, McPhaul M J, Hughes I A
Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, UK.
Baillieres Clin Endocrinol Metab. 1994 Apr;8(2):379-404. doi: 10.1016/s0950-351x(05)80258-7.
In a relatively short period of time, understanding of the fundamental causes of androgen insensitivity syndromes has improved dramatically. This has been brought about by the combination of several disciplines, including endocrinology, genetics, developmental and molecular biology. Mutations can be identified in the androgen receptor gene in suspected cases of AIS, and their functional consequences examined in various in-vitro systems. This information can then be correlated with the clinical presentation of the patient, and is beginning to provide an explanation for the highly variable clinical presentation of AIS. It is to be hoped that this information will also help to predict the likely outcome of androgen therapy in infants with PAIS and an intersex phenotype. More speculatively, functional studies may also lead to novel strategies for the treatment of patients. This would then be of enormous benefit to both patient and parents. Furthermore, the identification of a mutation allows precise information for genetic counselling of families affected by AIS. However, many questions still remain to challenge clinicians and scientists alike. These include the risk of testicular malignancy in patients with AIS and currently there is no worldwide consensus on the stage at which testes should be removed from patients reared as female. There are also significant challenges in patient counselling. Although there is greater understanding of the molecular defects that cause AIS, there are several examples of patients with a similar degree of receptor dysfunction, or even the same mutation, but whose phenotypes are widely different. Other factors must therefore contribute to the clinical presentation of AIS, although these have not been identified. Finally, there are the mutations in patients with Kennedy's disease. The consequences of the mutations are unexplained and are a clear indication that there is still a great deal to discover about the function and biology of androgen receptors.
在相对较短的时间内，对雄激素不敏感综合征根本病因的认识有了显著提高。这是由包括内分泌学、遗传学、发育生物学和分子生物学在内的多个学科共同作用实现的。在疑似雄激素不敏感综合征（AIS）的病例中，可以在雄激素受体基因中鉴定出突变，并在各种体外系统中检测其功能后果。然后，这些信息可以与患者的临床表现相关联，并开始为AIS高度可变的临床表现提供解释。希望这些信息也有助于预测患有部分雄激素不敏感综合征（PAIS）和两性畸形表型的婴儿接受雄激素治疗的可能结果。更具推测性的是，功能研究也可能带来治疗患者的新策略。这将对患者及其父母都有巨大益处。此外，突变的鉴定为受AIS影响的家庭提供了精确的遗传咨询信息。然而，许多问题仍然有待临床医生和科学家共同应对。这些问题包括AIS患者发生睾丸恶性肿瘤的风险，目前对于应该在什么阶段将睾丸从按女性抚养的患者体内切除，全球尚未达成共识。在患者咨询方面也存在重大挑战。尽管对导致AIS的分子缺陷有了更深入的了解，但有几个例子表明，受体功能障碍程度相似甚至具有相同突变的患者，其表型却大不相同。因此，其他因素必定也对AIS的临床表现有影响，尽管这些因素尚未被确定。最后，还有患有肯尼迪病患者的突变情况。这些突变的后果尚无法解释，这清楚地表明，关于雄激素受体的功能和生物学，仍有许多有待发现的地方。
