Characterization of a novel receptor mutation A↷T at exon 4 in complete androgen insensitivity syndrome and a carrier sibling via bidirectional polymorphism sequence analysis

  • Authors: E. Scott Sills, Thomas E. Sholes, Mark Perloe, Carolyn R. Kaplan, Jessica G. Davis, Michael J. Tucker
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  • Published online on: Tuesday, January 1, 2002
  • Pages: 45-48
  • DOI: 10.3892/ijmm.9.1.45

Abstract

The complete androgen insensitivity syndrome (AIS) is a sub-type of X-linked male pseudohermaphroditism resulting from total dysfunction of the androgen receptor. Affected patients are phenotypically female despite a 46,XY genotype; gonadal tissue displays a classic Sertoli cell-only pattern on microscopic examination. We describe the diagnosis and management of a 19½-year-old patient who presented for primary amenorrhea and absent cervix, identified incidentally during a routine Pap test. Serum total testosterone was elevated (725 ng/dl) and the karyotype was 46,XY. Molecular investigation for specific gene defect(s) causing disruption and functional incapacity of the androgen receptor was undertaken for the proband and her only sibling. From this we discovered a previously unknown hemizygous mutation (A↷T) in exon 4 of the androgen receptor gene, associated with replacement of asparagine (AAT) with tyrosine (TAT) in the resultant androgen receptor protein [N705Y]. Bidirectional, non-isotopic sequence analysis of exon 4 was next undertaken for the proband's sister who was found to be heterozygous for this mutation. Psychological and genetic counseling was provided to both individuals; the patient underwent an outpatient laparoscopic orchiectomy without complication. She continues to receive oral hormone replacement therapy following an oral contraceptive model. In this report, the clinical approach to AIS is outlined from a reproductive endocrinology perspective with special emphasis on psychological counseling and laboratory methods employed to confirm the diagnosis at the molecular level. We also outline other recently described mutations of the androgen receptor gene (Xq11-12) which have been associated with AIS.
Journal Cover

January 2002
Volume 9 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

2012 Impact Factor: 1.957
Ranked #26/121 Medicine Research and Experimental
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APA
Sills, E., Sholes, T., Perloe, M., Kaplan, C., Davis, J., & Tucker, M. (2002). Characterization of a novel receptor mutation A↷T at exon 4 in complete androgen insensitivity syndrome and a carrier sibling via bidirectional polymorphism sequence analysis. International Journal of Molecular Medicine, 9(1), 45-48.
MLA
Sills, Sholes, Perloe, Kaplan, Davis, and Michael Tucker. "Characterization of a novel receptor mutation A↷T at exon 4 in complete androgen insensitivity syndrome and a carrier sibling via bidirectional polymorphism sequence analysis." International Journal of Molecular Medicine International Journal of Molecular Medicine 9.1 (2002): 45-48.
Chicago
Sills, Sholes, Perloe, Kaplan, Davis, and Michael Tucker. "Characterization of a novel receptor mutation A↷T at exon 4 in complete androgen insensitivity syndrome and a carrier sibling via bidirectional polymorphism sequence analysis." International Journal of Molecular Medicine International Journal of Molecular Medicine 9 no. 1 (2002): 45-48.