雄激素受体基因突变患者雄激素敏感性的功能评估和临床分类。德国联合阴阳人研究小组。
文章的细节
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引用
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辛内克GH, Hiort O, Nitsche EM, Holterhus PM, Kruse K
雄激素受体基因突变患者雄激素敏感性的功能评估和临床分类。德国联合阴阳人研究小组。
欧洲儿科杂志。1997年1月;156(1):7-14。
- PubMed ID
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9007482 (在PubMed]
- 摘要
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在有基因的男性中,雄激素受体(AR)基因的突变导致了从女性到低生育能力男性的各种表型。生殖器皮肤成纤维细胞的结合试验和DNA分析仅提供受体功能的不完全信息。我们使用性激素结合球蛋白(SHBG)对斯坦诺唑尔的反应作为AR功能的衡量标准,并将结果与根据男性化缺陷程度分类的表型相关联。在调查的34例患者中,9例为完全雄激素不敏感综合征(AIS), 14例为部分雄激素不敏感综合征(AIS),表型以女性、模糊或男性为主。11名受试者作为对照。采用聚合酶链反应-单链构象多态性分析和直接DNA测序对突变进行表征。DNA分析发现了两个主要的缺失,两个导致外显子1过早停止密码子的小缺陷,以及AR基因的DNA和激素结合域的19个点突变。stanozolol治疗后,完全性AIS患者的SHBG保持不变(102.0 +/- 3.8 [SE]%;初始值的92.4%-129%)。部分AIS患者SHBG降低,以女性为主(83.8% +/- 1.7%; range 81.3%-87.0%), ambiguous (80.4% +/- 4.4%, range 68.4%-89.1%), and predominantly male (mean 65.9% +/- 4.9%, range 48.6%-80.8%) phenotypes, and normal in controls (51.4% +/- 2.1%, range 35.6%-62.1%). Differences between controls and each AIS group were statistically significant (P < 0.05 - < 0.0001). A close correlation was found between the degree of undermasculinization (AIS phenotype) and the SHBG response. CONCLUSIONS: The SHBG test provides functional information about the severity of the receptor defect in vivo and hence adds to the structural information provided by DNA analysis. It detects receptor defects due to mutations within the entire gene, including the DNA-binding domain, and is a rapid, simple, and cost effective procedure. It may provide useful information for the diagnosis and management of affected children.