Melo Caroline Oa, Silva Daniela M, da Cruz Aparecido D
Pontifícia Universidade Católica de Goiás, Departamento de Biologia, Núcleo de Pesquisas Replicon, Goiânia, Goiás, Brazil.
J Med Case Rep. 2011 Sep 8;5:446. doi: 10.1186/1752-1947-5-446.
Androgen is a generic term usually applied to describe a group of sex steroid hormones. Androgens are responsible for male sex differentiation during embryogenesis at the sixth or seventh week of gestation, triggering the development of the testes and penis in male fetuses, and are directed by the testicular determining factor: the gene SRY (sex determining region on Y chromosome) located on the short arm of chromosome Y. The differentiation of male external genitalia (penis, scrotum and penile urethra) occurs between the 9th and 13th weeks of pregnancy and requires adequate concentration of testosterone and the conversion of this to another more potent androgen, dihydrotestosterone, through the action of 5α-reductase in target tissues.
This report describes the case of a teenage girl presenting with a male karyotype, and aims to determine the extension of the mutation that affected the AR gene. A Caucasian girl aged 15 was referred to our laboratory for genetic testing due to primary amenorrhea. Physical examination, karyotype testing and molecular analysis of the androgen receptor were critical in making the correct diagnosis of complete androgen insensitivity syndrome.
Sex determination and differentiation depend on a cascade of events that begins with the establishment of chromosomal sex at fertilization and ends with sexual maturation at puberty, subsequently leading to fertility. Mutations affecting the AR gene may cause either complete or partial androgen insensitivity syndrome. The case reported here is consistent with complete androgen insensitivity syndrome, misdiagnosed at birth, and consequently our patient was raised both socially and educationally as a female. It is critical that health care providers understand the importance of properly diagnosing a newborn manifesting ambiguous genitalia. Furthermore, a child with a pseudohermaphrodite phenotype should always undergo adequate endocrine and genetic testing to reach a conclusive diagnosis before gender is assigned and surgical interventions are carried out. Our results show that extreme care must be taken in selecting the genetic tools that are utilized for the diagnosis for androgen insensitivity syndrome.
雄激素是一个通用术语，通常用于描述一组性类固醇激素。雄激素在妊娠第六或第七周的胚胎发育过程中负责男性性别分化，触发男性胎儿睾丸和阴茎的发育，并由睾丸决定因子指导：位于Y染色体短臂上的SRY基因（Y染色体性别决定区）。男性外生殖器（阴茎、阴囊和阴茎尿道）的分化发生在妊娠第9至13周之间，需要足够浓度的睾酮，并通过靶组织中5α-还原酶的作用将其转化为另一种更有效的雄激素双氢睾酮。
本报告描述了一名具有男性核型的青少年女孩的病例，旨在确定影响雄激素受体（AR）基因的突变范围。一名15岁的白种女孩因原发性闭经被转诊至我们实验室进行基因检测。体格检查、核型检测和雄激素受体的分子分析对于正确诊断完全性雄激素不敏感综合征至关重要。
性别决定和分化取决于一系列事件，始于受精时染色体性别的确定，止于青春期的性成熟，随后导致生育能力。影响AR基因的突变可能导致完全或部分雄激素不敏感综合征。此处报告的病例与完全性雄激素不敏感综合征一致，出生时被误诊，因此我们的患者在社会和教育方面均被当作女性抚养。医疗保健提供者了解正确诊断表现为生殖器模糊的新生儿的重要性至关重要。此外，具有假两性畸形表型的儿童在进行性别分配和手术干预之前，应始终接受充分的内分泌和基因检测以得出确定性诊断。我们的结果表明，在选择用于诊断雄激素不敏感综合征的基因工具时必须极其谨慎。
