An Uncommon Large Deletion in the Androgen-receptor Gene in a XY Female with Complete Androgen Insensitivity Syndrome

Overview

Journal J Endocrinol Invest

Publisher Springer

Specialty Endocrinology

Date 2006 Jun 24

PMID 16794370

Authors

C Moretti

T Odorisio

R Geremia

P Grimaldi

Affiliations

Soon will be listed here.

Abstract

Androgen insensitivity is a disorder characterized by an abnormal male sexual development, in which the androgen action is impaired due to structural defects in the androgen receptor gene. We report a case of a 46,XY subject with female phenotype (normal breast and external genitalia) lacking sexual hair, affected with primary amenorrhea. In this patient, we found a deletion of a large region of the androgen receptor gene encoding the steroid-binding domain of the protein, causing a complete inability to bind the androgens. This uncommon molecular defect impaired the expression of androgen-dependent genes inducing the female phenotype.

References

Kawate H, Wu Y, Ohnaka K, Tao R, Nakamura K, Okabe T . Impaired nuclear translocation, nuclear matrix targeting, and intranuclear mobility of mutant androgen receptors carrying amino acid substitutions in the deoxyribonucleic acid-binding domain derived from androgen insensitivity syndrome patients. J Clin Endocrinol Metab. 2005; 90(11):6162-9. DOI: 10.1210/jc.2005-0179. View

Black B, Paschal B . Intranuclear organization and function of the androgen receptor. Trends Endocrinol Metab. 2004; 15(9):411-7. DOI: 10.1016/j.tem.2004.09.006. View

Morris J . The syndrome of testicular feminization in male pseudohermaphrodites. Am J Obstet Gynecol. 1953; 65(6):1192-1211. DOI: 10.1016/0002-9378(53)90359-7. View

Quigley C, De Bellis A, Marschke K, El-Awady M, Wilson E, French F . Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr Rev. 1995; 16(3):271-321. DOI: 10.1210/edrv-16-3-271. View

Brown T . Androgen receptor dysfunction in human androgen insensitivity. Trends Endocrinol Metab. 1995; 6(5):170-5. DOI: 10.1016/1043-2760(95)00082-s. View

French F, Van Wyk J, Baggett B, Easterling W, TALBERT L, JOHNSTON F . Further evidence of a target organ defect in the syndrome of testicular feminization. J Clin Endocrinol Metab. 1966; 26(5):493-503. DOI: 10.1210/jcem-26-5-493. View

Brown C, Goss S, Lubahn D, Joseph D, Wilson E, French F . Androgen receptor locus on the human X chromosome: regional localization to Xq11-12 and description of a DNA polymorphism. Am J Hum Genet. 1989; 44(2):264-9. PMC: 1715398. View

Gottlieb B, Beitel L, Wu J, Trifiro M . The androgen receptor gene mutations database (ARDB): 2004 update. Hum Mutat. 2004; 23(6):527-33. DOI: 10.1002/humu.20044. View

Gottlieb B, Lombroso R, Beitel L, Trifiro M . Molecular pathology of the androgen receptor in male (in)fertility. Reprod Biomed Online. 2005; 10(1):42-8. DOI: 10.1016/s1472-6483(10)60802-4. View

10.

Adachi M, Takayanagi R, Tomura A, Imasaki K, Kato S, Goto K . Androgen-insensitivity syndrome as a possible coactivator disease. N Engl J Med. 2000; 343(12):856-62. DOI: 10.1056/NEJM200009213431205. View

11.

French F, Spooner I, Baggett B . Metabolism of 17-hydroxyprogesterone in testicular tissue from a patient with the syndrome of testicular feminization. J Clin Endocrinol Metab. 1967; 27(3):437-9. DOI: 10.1210/jcem-27-3-437. View

12.

Strickland A, French F . Absence of response to dihydrotestosterone in the syndrome of testicular feminization. J Clin Endocrinol Metab. 1969; 29(9):1284-6. DOI: 10.1210/jcem-29-9-1284. View

13.

Heinlein C, Chang C . Androgen receptor (AR) coregulators: an overview. Endocr Rev. 2002; 23(2):175-200. DOI: 10.1210/edrv.23.2.0460. View

14.

Conn J, Gillam L, Conway G . Revealing the diagnosis of androgen insensitivity syndrome in adulthood. BMJ. 2005; 331(7517):628-30. PMC: 1215563. DOI: 10.1136/bmj.331.7517.628. View

15.

GRIFFIN J . Androgen resistance--the clinical and molecular spectrum. N Engl J Med. 1992; 326(9):611-8. DOI: 10.1056/NEJM199202273260906. View

16.

Mazen I, Lumbroso S, Abdel Ghaffar S, Salah N, Sultan C . Mutation of the androgen receptor (R840S) in an Egyptian patient with partial androgen insensitivity syndrome: review of the literature on the clinical expression of different R840 substitutions. J Endocrinol Invest. 2004; 27(1):57-60. DOI: 10.1007/BF03350912. View

17.

Brown T, Lubahn D, Wilson E, Joseph D, French F, Migeon C . Deletion of the steroid-binding domain of the human androgen receptor gene in one family with complete androgen insensitivity syndrome: evidence for further genetic heterogeneity in this syndrome. Proc Natl Acad Sci U S A. 1988; 85(21):8151-5. PMC: 282385. DOI: 10.1073/pnas.85.21.8151. View

18.

GOTTLIEB B, Beitel L, Trifiro M . Somatic mosaicism and variable expressivity. Trends Genet. 2001; 17(2):79-82. DOI: 10.1016/s0168-9525(00)02178-8. View

19.

Bradford M . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54. DOI: 10.1016/0003-2697(76)90527-3. View

20.

McPhaul M, Marcelli M, Zoppi S, GRIFFIN J, Wilson J . Genetic basis of endocrine disease. 4. The spectrum of mutations in the androgen receptor gene that causes androgen resistance. J Clin Endocrinol Metab. 1993; 76(1):17-23. DOI: 10.1210/jcem.76.1.8421085. View