A frame shift mutation in the DNA-binding domain of the androgen receptor gene associated with complete androgen insensitivity, persistent müllerian structures, and germ cell tumors in dysgenetic gonads.

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.

METHODS

Descriptive case study.

METHODS

Mackay Memorial Hospital and National Yang-Ming University, Taipei, Taiwan.

METHODS

A 22-year-old 46,XY female with persistent müllerian structures, a low level of serum testosterone, and no apparent adnexal masses.

METHODS

Laparoscopic removal of the dysgenetic gonads.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.