New mutation causing androgen insensitivity syndrome – a case report and review of literature

Abstract

Androgen insensitivity syndrome (AIS) is a congenital disorder in which a defect in the androgen receptor (AR) gene leads to cellular resistance to androgens. Defects in the AR gene, located on the X chromosome, result in the development of a feminine phenotype in chromosomally male (46, XY) individuals. In this case report, we present a 44 years old patient with complete androgen insensitivity syndrome (CAIS) initially presenting with primary amenorrhea. The patient underwent a full clinical evaluation, revealing hypoplastic vagina and a lack of uterus and ovaries. Hormonal evaluation revealed markedly elevated testosterone, FSH, and LH serum concentrations. Diagnostic imaging, including pelvic MRI, confirmed the presence of two solid masses in the inguinal canals (right 26 × 13 mm, left 25 × 15 mm). The patient underwent genetic testing, revealing a 46 XY karyotype and an as of yet unprecedented androgen receptor mutation. The type of the mutation was a single-base exchange – the substitution from cytosine to thymine in chromosome X:66942710 position (referred to human reference genome GRCh37), which has resulted in an amino acid changes from leucine (CTT) to phenyloalanine (TTT) in ligand-binding domain.

摘要

雄激素不敏感综合征（AIS）是一种由于雄激素受体（AR）基因缺陷而导致细胞对雄激素抵抗的先天性疾病。由于位于X染色体上AR基因的缺失, 导致在染色体男性（46, XY）个体中形成女性表型。在这个个案报道中, 我们报告了一位44岁的完全型雄激素不敏感综合征(CAIS)的患者, 她最初表现为原发性闭经。我们对这个患者进行了全面的临床检查, 发现阴道发育不良, 并且子宫和卵巢缺如。激素检测显示血清中睾酮、FSH和LH浓度明显升高。影像学诊断包括盆腔MRI, 证实在腹股沟区有两个实性包块（右侧26 × 13mm, 左侧25 × 15mm）。对这个患者进行了基因检测, 发现染色体核型为46XY并且是由于一个从未被发现的雄激素受体的缺陷所到导致。突变类型为单碱基交换- X染色体66942710位(参照人类参考基因组GRCh37)胞嘧啶取代胸腺嘧啶, 导致配体结合域氨基酸由亮氨酸(CTT)转变为苯丙氨酸(TTT)

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• androgen insensitivity syndrome
• Morris syndrome
• androgen receptor
• disorders of sex development
• 46
• XY

Disclosure statement

No potential conflict of interest was reported by the authors.