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.
Chen
C P
CP
Department of Obstetrics and Gynecology, Mackay Memorial Hospital and National Yang-Ming University, Taipei, Taiwan, Republic of China. cpcvmmh@yahoo.com
Chen
S R
SR
Wang
T Y
TY
Wang
W
W
Hwu
Y M
YM
D000328:Adult; D013734:Androgen-Insensitivity Syndrome / Q000150:complications / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D004407:Dysgerminoma / Q000150:complications / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006059:Gonadal Dysgenesis / Q000150:complications / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D008297:Male; D009095:Mullerian Ducts / Q000002:abnormalities*; D009373:Neoplasms, Germ Cell and Embryonal / Q000150:complications / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*
D004268:DNA-Binding Proteins; D011944:Receptors, Androgen