A Novel Mutation of Androgen Receptor Gene in Complete Androgen Insensitivity Syndrome

abdominal testes at the time of repair of bilateral inguinal hernia in infancy. At the age of 9 yr, the patient together with her mother visited our service to consult about the pathogenesis. The maternal uncle, reportedly, has “undervirilized external genitalia”. The mother declined to tell further family history. On examination, the patient’s height was 133.2 cm (≅25th percentile) and weight 44.7 kg (>97th percentile). She had normal female external genitalia. No tumor was palpable around the inguinal area. Breast as well as pubic hair were Tanner I. Operation scars were present on the abdominal wall. Endocrinological studies were as follows: serum LH, 0.3 mIU/mL (normal); FSH 3.7 mIU/mL (normal); testosterone 0.20 ng/ml (normal), which was increased to 1.82 ng/ml by hCG stimulation (3,000 IU/m2/dose i.m. for three consecutive days, blood sampling on day 4). Her karyotype was 46,XY. Pelvic MRI revealed the right testis in the abdominal cavity and the left one in the inguinal canal. The patient was clinically diagnosed as having complete AIS. Written informed consent for a genetic study of the AR gene for the patient, but not for the parents, was obtained from her parents. This study was approved by the ethical committee of our institution. Genomic DNA was extracted from the patient’s peripheral lymphocytes. The AR coding region and flanking intronic sequences of all the exons were amplified by PCR, followed by direct sequencing as previously described (6). A hemizygous mutation (c.2125G>A, p.E709K) Androgen insensitivity syndrome (AIS) is an X-linked recessive disorder caused by mutation in the gene for the androgen receptor (AR) with 46,XY karyotype (OMIM 300068). The clinical phenotype of AIS is complete or partial. Complete AIS is characterized by a consistent phenotype: unambiguous female external genitalia, breast development at pubertal age, blind-ending vagina, absence of uterus, absent or scant pubic and axillary hair, and presence of normally differentiated testes in a girl or woman. However, the clinical features of partial AIS are variable: ambiguous external genitalia in a girl or woman, undervirilized external genitalia in a boy or man, or azospermia with unambiguous male external genitalia in a man (1–4). So far more than 300 mutations in all exons of the AR gene have been reported in complete AIS (5). We report a novel mutation of the AR gene in a patient with complete AIS.