Genetic analysis of a family with complete androgen insensitivity syndrome
A 10-year-old girl, product of consanguineous marriage was referred for evaluation of palpable gonads in the inguinal region. She was born at term after an uneventful pregnancy by normal vaginal delivery with a birth weight of 2.6 kg and length of 48 cm. Bilateral inguinal gonads with short and blind ended vagina were detected at birth. She was followed-up over a period of 8 months when assignment of the female gender was decided; corrective procedure for inguinal gonads was planned, but did not occur. On physical examination, she had typical female external genitalia. Palpable gonads were found bilaterally in the inguinal region [], pubertal stage was B4P5. The uterus was absent under pelvic sonograms. Hormonal evaluation revealed follicle stimulating hormone (5.4 mIU/mL; normal: 1.5-12.4), luteinizing hormone (21.2 mIU/mL; Normal: 1.7-8.6) and total testosterone (15 ng/mL; Normal: 2.86-8.1); chromosomal analysis showed diploid 46 XY karyotype. Testosterone and DHT synthesis defects were excluded by the normal rise of T and DHT after human chorionic gonadotrophin (HCG) stimulation (basal T: 15 ng/mL; basal DHT: 9.3 ng/mL, T/DHT ratio after HCG stimulation: 7:9). Gonadectomy was performed a few months later and histological analysis revealed bilateral testes with no evidence of malignancy. She subsequently underwent vaginoplasty and received therapy with estrogens. Three maternal aunts presented with primary amenorrhea with an adequate breast and pubic hair development and palpable gonads in the age group between 15 and 20 years and were treated with bilateral gonadectomy, vaginal reconstruction and estrogen supplementation.\nPeripheral blood samples were obtained from the girl and her maternal family members for molecular analysis. Genomic DNA was extracted with the use of polymerase chain reaction (PCR) amplification of AR exonic fragments 1-8 followed by direct sequencing analysis of the PCR products was performed. It revealed C 2754 to T transition in exon 6 []. The same mutation was confirmed in her mother and the 3 maternal aunts [], maternal grandmother []. Her mother and maternal grandmother were fertile carriers with 46 XX karyotype.