278例临床报告的雄激素不敏感综合征的表型特征、雄激素受体结合和突变分析。
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Ahmed SF, Cheng A, Dovey L, Hawkins JR, Martin H, Rowland J，志村N, Tait AD, Hughes IA
278例临床报告的雄激素不敏感综合征的表型特征、雄激素受体结合和突变分析。
中华临床内分泌杂志2000年2月;85(2):658-65。
- PubMed ID
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10690872 (在PubMed］
- 摘要
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雄激素不敏感综合征(AIS)是导致男性阳刚化不足的最常见的单一因素，但对AIS的大规模队列研究很少进行。在过去的十年中，英国儿科内分泌学家之间的全国性合作已允许创建一个阴阳人和生殖器模糊的病例数据库，通过问卷收集每个通报病例的详细临床信息。截至1999年1月，共有816项记录，其中105例临床诊断为完全AIS (CAIS)， 173例为部分AIS (PAIS)。通过对外部表现型的评分，设计了一个阳刚化评分，12分代表正常的阳刚化。通过研究结合能力(Bmax)和受体亲和力(K(d))来确定雄激素受体(AR)结合，将病例分为零结合、异常结合和正常结合。采用单链构象多态性分析对AR基因的8个外显子进行突变筛选，然后直接进行DNA测序。所有PAIS病例均在出生后第一个月内出现。CAIS患儿出现的中位年龄为1岁(P10,P90: 0.1,10.4)。在77%的CAIS和41%的PAIS病例中，睾丸可在阴唇皱襞或腹股沟区触摸到。被培养为女孩的PAIS儿童[2.5(P10, p90: 1,6)]与被培养为男孩的PAIS儿童[3(P10, p90: 2,7.5)]的阳刚化得分有显著重叠。 Gonadectomy was performed prepubertally in 66% and postpubertally in 29% of the cases of CAIS. The median age of the latter group was older at 14 yr (P10,P90:0.1,18). No cases of malignancy or carcinoma in situ were reported in the 121 cases of AIS where histology results were available. Biochemical endocrine investigations were reported to have been performed in a greater number of cases of PAIS than CAIS (98% vs. 48%). AR binding was abnormal in 44 of 51 (86%) and 40 of 113 (35%) cases of CAIS and PAIS, respectively. Zero binding was encountered in 29 of 43 (67%) and 1 of 55 (2%) cases of CAIS and PAIS, respectively. Mutational analysis of the AR gene, performed in 102 index cases was positive in 57 of 69 (83%) cases of CAIS and 12 of 43 (28%) cases of PAIS. In 24 of these cases, the mutation identified was novel. The mutations in PAIS cases were all missense, whereas in CAIS the mutations were more diverse. AR binding was only normal in 3 of 69 mutation-positive cases. In the PAIS group, mutation-positive cases had a significantly higher Kd and Bmax compared to the mutation negative cases. The clinical diagnosis of AIS can be confirmed in a significant number of cases by a combination of androgen-binding studies and mutational analysis. There is some correlation between the phenotypic features and the abnormalities discovered on mutational analysis of the AR gene, but there is a need to improve this further by developing optimal bioassays of AR function. The phenotypic heterogeneity among clinically diagnosed cases of AIS emphasizes the need for appropriate comprehensive evaluation of male under-masculinization.