Abstract：
BACKGROUND: Androgen insensitivity syndrome (AIS) is a common condition among individuals with differences of sexual development (DSD) and results from germline allelic variants in the androgen receptor (AR) gene. Understanding the phenotypic consequences of AR allelic variants that disrupt the activation function 2 (AF2) region is essential to grasping its clinical significance.
OBJECTIVE: This study aims to provide insights into the phenotypic characteristics and clinical impact of AR mutations affecting the AF2 region in AIS patients. We achieve this by reviewing reported AR variants in the AF2 region among individuals with AIS, including identifying a new phenotype associated with the c.2138T>C variant (p.Leu713Pro) in the AR gene.
METHODS: We comprehensively reviewed AR variants within the AF2 region reported in AIS and applied molecular dynamics simulations to assess the impact of the p.Leu713Pro variant on protein dynamics.
RESULTS: Our review of reported AR variants in the AF2 region revealed a spectrum of phenotypic outcomes in AIS patients. Molecular dynamics simulations indicated that the p.Leu713Pro variant significantly alters the local dynamics of the AR protein and disrupts the correlation and covariance between variables.
CONCLUSIONS: The diverse phenotypic presentations observed among individuals with AR variants in the AF2 region highlight the complexity of AIS. The altered protein dynamics resulting from the p.Leu713Pro variant further emphasize the importance of the AF2 region in AR function.
CONCLUSIONS: Our study provides valuable insights into AR mutations\' phenotypic characteristics and clinical impact on the AF2 region in AIS. Moreover, the disruption of protein dynamics underscores the significance of the AF2 region in AR function and its role in the pathogenesis of AIS.
OBJECTIVE: This study aims to provide insights into the phenotypic characteristics and clinical impact of AR mutations affecting the AF2 region in AIS patients. We achieve this by reviewing reported AR variants in the AF2 region among individuals with AIS, including identifying a new phenotype associated with the c.2138T>C variant (p.Leu713Pro) in the AR gene.
METHODS: We comprehensively reviewed AR variants within the AF2 region reported in AIS and applied molecular dynamics simulations to assess the impact of the p.Leu713Pro variant on protein dynamics.
RESULTS: Our review of reported AR variants in the AF2 region revealed a spectrum of phenotypic outcomes in AIS patients. Molecular dynamics simulations indicated that the p.Leu713Pro variant significantly alters the local dynamics of the AR protein and disrupts the correlation and covariance between variables.
CONCLUSIONS: The diverse phenotypic presentations observed among individuals with AR variants in the AF2 region highlight the complexity of AIS. The altered protein dynamics resulting from the p.Leu713Pro variant further emphasize the importance of the AF2 region in AR function.
CONCLUSIONS: Our study provides valuable insights into AR mutations\' phenotypic characteristics and clinical impact on the AF2 region in AIS. Moreover, the disruption of protein dynamics underscores the significance of the AF2 region in AR function and its role in the pathogenesis of AIS.
摘要：
背景：雄激素不敏感综合征（AIS）是具有性发育差异（DSD）的个体中的常见病，是由雄激素受体（AR）基因的种系等位基因变异引起的。了解破坏激活功能2（AF2）区域的AR等位基因变体的表型后果对于掌握其临床意义至关重要。
目的：本研究旨在深入了解影响AIS患者AF2区的AR突变的表型特征和临床影响。我们通过回顾AIS个体中AF2区域的AR变异来实现这一目标，包括鉴定与c.2138T>C变体相关的新表型(p.Leu713Pro)在AR基因中。
方法：我们全面回顾了AIS中报道的AF2区域内的AR变体，并应用分子动力学模拟来评估p.Leu713Pro变体对蛋白质动力学的影响。
结果：我们对报道的AF2区AR变异的综述揭示了AIS患者的一系列表型结果。分子动力学模拟表明p.Leu713Pro变体显着改变AR蛋白的局部动力学并破坏变量之间的相关性和协方差。
结论：在AF2区具有AR变异的个体中观察到的不同表型表现突出了AIS的复杂性。由p.Leu713Pro变体产生的改变的蛋白质动力学进一步强调了AF2区在AR功能中的重要性。
结论：我们的研究为AR突变的表型特征和对AIS中AF2区的临床影响提供了有价值的见解。此外，蛋白质动力学的破坏强调了AF2区在AR功能中的重要性及其在AIS发病机理中的作用。
目的：本研究旨在深入了解影响AIS患者AF2区的AR突变的表型特征和临床影响。我们通过回顾AIS个体中AF2区域的AR变异来实现这一目标，包括鉴定与c.2138T>C变体相关的新表型(p.Leu713Pro)在AR基因中。
方法：我们全面回顾了AIS中报道的AF2区域内的AR变体，并应用分子动力学模拟来评估p.Leu713Pro变体对蛋白质动力学的影响。
结果：我们对报道的AF2区AR变异的综述揭示了AIS患者的一系列表型结果。分子动力学模拟表明p.Leu713Pro变体显着改变AR蛋白的局部动力学并破坏变量之间的相关性和协方差。
结论：在AF2区具有AR变异的个体中观察到的不同表型表现突出了AIS的复杂性。由p.Leu713Pro变体产生的改变的蛋白质动力学进一步强调了AF2区在AR功能中的重要性。
结论：我们的研究为AR突变的表型特征和对AIS中AF2区的临床影响提供了有价值的见解。此外，蛋白质动力学的破坏强调了AF2区在AR功能中的重要性及其在AIS发病机理中的作用。
