Objective: To describe the molecular, cytogenetic, immunohistochemical, and endocrinologic characteristics of a young 46,XY female with persistent müllerian structures and germ cell tumors in dysgenetic gonads.
Design: Descriptive case study.
Setting: Mackay Memorial Hospital and National Yang-Ming University, Taipei, Taiwan.
Patient(s): A 22-year-old 46,XY female with persistent müllerian structures, a low level of serum testosterone, and no apparent adnexal masses.
Intervention(s): Laparoscopic removal of the dysgenetic gonads.
Main outcome measure(s): Detection of an androgen receptor gene mutation by a semiautomated DNA sequencer, of the chromosomal complement by cytogenetic examination, of placental alkaline phosphatase activity by immunohistochemical analysis, and of neoplasms in dysgenetic gonads by histologic studies.
Result(s): A unilateral gonadoblastoma and a contralateral gonadoblastoma associated with a dysgerminoma were found in the excised gonads. The tumors had a 46,XY complement. Placental alkaline phosphatase was present in the tumor cells. A frameshift mutation in the DNA-binding domain of the androgen receptor gene was detected in the patient's blood and the tumor tissues. A five-nucleotide "AGGAA" deletion at codons 608 and 609 of the androgen receptor gene resulted in a missing arginine and lysine as well as a frameshift that introduced a stop codon 12 amino acid downstream from the mutation.
Conclusion(s): Molecular genetic analysis of the androgen receptor gene aids in the rapid diagnosis of complete androgen insensitivity irrespective of atypical clinical phenotypes and endocrinologic parameters.