Abstract：
BACKGROUND: Androgen insensitivity syndrome (AIS) manifests itself as variable symptoms of under-virilization in patients with 46,XY disorders caused by androgen receptor (AR) gene variants. This large-sample study aimed to correlate the genotypes and phenotypes to the fertility of individuals.
METHODS: This was a cohort study that analyzed the genetic and clinical characteristics of patients with AIS from a single center in China.
RESULTS: The 117 patients were divided into 53 with complete AIS (CAIS) and 64 with partial AIS (PAIS). At their first visit, the median age was 1.83 years (0.92-4.17), and the external masculinization score was 3.0 (2.0-6.0). At the last follow-up, 92% (49/53) of patients with CAIS maintained their female gender, and 94% (60/64) of patients with PAIS were raised as males. No gender anxiety was observed in this study. Eighty-eight AR variants were identified, with 31 (35%) being unreported. Moreover, 24% (21/88) occurred more than once. The variants that appeared most frequently were located at amino acid 841, including p.R841H (n = 5) and p.R841C (n = 2). Variants p.N706S, p.R856H, and p.A871V were each observed 4 times. In terms of inheritance, 83% of patients with parental verification inherited variants from their mothers. We also observed that the variants from 1 case were inherited from his maternal grandfather who had hypospadias.
CONCLUSIONS: Most children with PAIS were raised as males. The abundance of maternally inheritable variants and the presence of case of preserved fertility indicate the fertility potential in patients with AIS. Hence, we recommend a careful evaluation of gonadectomy when fertility preservation is being considered.
METHODS: This was a cohort study that analyzed the genetic and clinical characteristics of patients with AIS from a single center in China.
RESULTS: The 117 patients were divided into 53 with complete AIS (CAIS) and 64 with partial AIS (PAIS). At their first visit, the median age was 1.83 years (0.92-4.17), and the external masculinization score was 3.0 (2.0-6.0). At the last follow-up, 92% (49/53) of patients with CAIS maintained their female gender, and 94% (60/64) of patients with PAIS were raised as males. No gender anxiety was observed in this study. Eighty-eight AR variants were identified, with 31 (35%) being unreported. Moreover, 24% (21/88) occurred more than once. The variants that appeared most frequently were located at amino acid 841, including p.R841H (n = 5) and p.R841C (n = 2). Variants p.N706S, p.R856H, and p.A871V were each observed 4 times. In terms of inheritance, 83% of patients with parental verification inherited variants from their mothers. We also observed that the variants from 1 case were inherited from his maternal grandfather who had hypospadias.
CONCLUSIONS: Most children with PAIS were raised as males. The abundance of maternally inheritable variants and the presence of case of preserved fertility indicate the fertility potential in patients with AIS. Hence, we recommend a careful evaluation of gonadectomy when fertility preservation is being considered.
摘要：
背景：雄激素不敏感综合征（AIS）表现为由雄激素受体（AR）基因变异引起的46,XY疾病患者缺乏男性化的可变症状。这项大样本研究旨在将基因型和表型与个体的生育力相关联。
方法：这是一项队列研究，分析了来自中国单个中心的AIS患者的遗传和临床特征。
结果：117例患者分为完全AIS（CAIS）53例和部分AIS（PAIS）64例。首次就诊时，中位年龄为1.83岁（0.92-4.17），EMS为3.0（2.0-6.0）。在最后一次随访中，92%(49/53)的CAIS患者保持其女性性别，94%(60/64)的PAIS患者为男性。在这项研究中没有观察到性别焦虑。确定了88个AR变体，31人（35%）未报告。此外，24%(21/88)发生过一次以上。最频繁出现的变体位于氨基酸841,包括p.R841H(n=5)和p.R841C(n=2)。Variantsp.N706S,p.R856H,和p.A871V各观察4次。在继承方面,83％的父母验证患者从母亲那里继承了变异。我们还观察到，一个病例的变异是继承自患有尿道下裂的外祖父。
结论：大多数患有PAIS的儿童都是男性长大的。大量的母系遗传变异和保留生育能力的存在表明AIS患者的生育能力潜力。因此，我们建议在考虑保留生育能力时仔细评估性腺切除术.
方法：这是一项队列研究，分析了来自中国单个中心的AIS患者的遗传和临床特征。
结果：117例患者分为完全AIS（CAIS）53例和部分AIS（PAIS）64例。首次就诊时，中位年龄为1.83岁（0.92-4.17），EMS为3.0（2.0-6.0）。在最后一次随访中，92%(49/53)的CAIS患者保持其女性性别，94%(60/64)的PAIS患者为男性。在这项研究中没有观察到性别焦虑。确定了88个AR变体，31人（35%）未报告。此外，24%(21/88)发生过一次以上。最频繁出现的变体位于氨基酸841,包括p.R841H(n=5)和p.R841C(n=2)。Variantsp.N706S,p.R856H,和p.A871V各观察4次。在继承方面,83％的父母验证患者从母亲那里继承了变异。我们还观察到，一个病例的变异是继承自患有尿道下裂的外祖父。
结论：大多数患有PAIS的儿童都是男性长大的。大量的母系遗传变异和保留生育能力的存在表明AIS患者的生育能力潜力。因此，我们建议在考虑保留生育能力时仔细评估性腺切除术.
