Severe forms of complete androgen insensitivity syndrome caused by a p.Q65X novel mutation in androgen receptor: Clinical manifestations, imaging findings and molecular genetics

Androgen insensitivity syndrome (AIS), a rare X-linked recessive genetic disorder with a normal 46, XY karyotype, is caused by defect of androgen receptor gene (AR) leading to resistance of the target tissues to androgenic hormones. There is a wide spectrum of clinical presentations of AIS, ranging from male infertility, hypospadias to completely normal female external genitalia. Here, we describe a 15-year old, phenotypically female individual, who visited our clinic for primary amenorrhea. The physical examination revealed normal female external genitalia, normal breast development, as well as sparse pubic hair and absence of axillary hair. A short blind vagina pouch was noticed in gynecological examination apart from the absence of cervix and uterus. Serum testosterone measured a considerable high level, and the karyotype was indicative of a normal male (46, XY). Transabdominal ultrasound (US) and magnetic resonance imaging (MRI) confirmed the absence of uterus, ovaries and fallopian tubes, only with a small blind-ending vagina observed. The clinical, laboratory, imaging, and genetic findings strongly suggest the diagnosis of complete androgen insensitivity syndrome (CAIS). Mutational analysis of the AR gene revealed a novel small insertion mutation c.192_193insTAGCAG(Q65X) in exon 1, which gives rise to a truncated nonfunctional protein, resulting in the loss of the remaining 856 C-terminus amino acid residues. This study indicates that US and MRI are two useful and noninvasive imaging methods for the diagnosis and evaluation of CAIS, and identification of this novel mutation expands the database of AR gene mutations. Furthermore, with the availability of the identification technology for this mutation, prenatal diagnosis could be offered for future pregnancies.