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. 1993 Apr;68(4):453–457. doi: 10.1136/adc.68.4.453

Phenotypic variation and detection of carrier status in the partial androgen insensitivity syndrome.

J A Batch 1, H R Davies 1, B A Evans 1, I A Hughes 1, M N Patterson 1
PMCID: PMC1029262  PMID: 8099270

Abstract

The partial androgen insensitivity syndrome occurs in 46,XY subjects with phenotypes ranging from perineoscrotal hypospadias with cryptorchidism and micropenis (mild undervirilisation) to clitoromegaly and partial labial fusion (marked undervirilisation). Within an affected family, wide variation in the degree of genital ambiguity between individuals can be seen. Two cousins of a previously reported subject who had severe genital ambiguity and partial androgen insensitivity were investigated. Neither of the cousins had genital abnormalities as marked as the index case, who also had qualitatively abnormal androgen binding and two mutations of the androgen receptor gene. Despite marked phenotypic differences between the index case and his cousins, similar androgen binding and the same androgen receptor mutations were shown in the cousins. Furthermore, one of the androgen receptor gene mutations has been shown in the mother and sister of one of the boys indicating that they are carriers. Thus phenotypic variation in families affected by partial androgen insensitivity is dependent on factors other than abnormalities of the androgen receptor gene alone. Although carrier status in partial androgen insensitivity can be determined, the severity of genital abnormalities in an affected offspring cannot be reliably predicted.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Batch J. A., Williams D. M., Davies H. R., Brown B. D., Evans B. A., Hughes I. A., Patterson M. N. Androgen receptor gene mutations identified by SSCP in fourteen subjects with androgen insensitivity syndrome. Hum Mol Genet. 1992 Oct;1(7):497–503. doi: 10.1093/hmg/1.7.497. [DOI] [PubMed] [Google Scholar]
  2. Brown C. J., Goss S. J., Lubahn D. B., Joseph D. R., Wilson E. M., French F. S., Willard H. 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 Feb;44(2):264–269. [PMC free article] [PubMed] [Google Scholar]
  3. Chang C. S., Kokontis J., Liao S. T. Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science. 1988 Apr 15;240(4850):324–326. doi: 10.1126/science.3353726. [DOI] [PubMed] [Google Scholar]
  4. Edwards A., Hammond H. A., Jin L., Caskey C. T., Chakraborty R. Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups. Genomics. 1992 Feb;12(2):241–253. doi: 10.1016/0888-7543(92)90371-x. [DOI] [PubMed] [Google Scholar]
  5. Evans B. A., Jones T. R., Hughes I. A. Studies of the androgen receptor in dispersed fibroblasts: investigation of patients with androgen insensitivity. Clin Endocrinol (Oxf) 1984 Jan;20(1):93–105. doi: 10.1111/j.1365-2265.1984.tb00063.x. [DOI] [PubMed] [Google Scholar]
  6. Grino P. B., Isidro-Gutierrez R. F., Griffin J. E., Wilson J. D. Androgen resistance associated with a qualitative abnormality of the androgen receptor and responsive to high dose androgen therapy. J Clin Endocrinol Metab. 1989 Mar;68(3):578–584. doi: 10.1210/jcem-68-3-578. [DOI] [PubMed] [Google Scholar]
  7. Hughes I. A., Evans B. A. Androgen insensitivity in forty-nine patients: classification based on clinical and androgen receptor phenotypes. Horm Res. 1987;28(1):25–29. doi: 10.1159/000180921. [DOI] [PubMed] [Google Scholar]
  8. Jenster G., van der Korput H. A., van Vroonhoven C., van der Kwast T. H., Trapman J., Brinkmann A. O. Domains of the human androgen receptor involved in steroid binding, transcriptional activation, and subcellular localization. Mol Endocrinol. 1991 Oct;5(10):1396–1404. doi: 10.1210/mend-5-10-1396. [DOI] [PubMed] [Google Scholar]
  9. Lubahn D. B., Joseph D. R., Sullivan P. M., Willard H. F., French F. S., Wilson E. M. Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science. 1988 Apr 15;240(4850):327–330. doi: 10.1126/science.3353727. [DOI] [PubMed] [Google Scholar]
  10. McPhaul M. J., Marcelli M., Tilley W. D., Griffin J. E., Isidro-Gutierrez R. F., Wilson J. D. Molecular basis of androgen resistance in a family with a qualitative abnormality of the androgen receptor and responsive to high-dose androgen therapy. J Clin Invest. 1991 Apr;87(4):1413–1421. doi: 10.1172/JCI115147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. McPhaul M. J., Marcelli M., Tilley W. D., Griffin J. E., Wilson J. D. Androgen resistance caused by mutations in the androgen receptor gene. FASEB J. 1991 Nov;5(14):2910–2915. doi: 10.1096/fasebj.5.14.1752359. [DOI] [PubMed] [Google Scholar]
  12. Orita M., Suzuki Y., Sekiya T., Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. doi: 10.1016/0888-7543(89)90129-8. [DOI] [PubMed] [Google Scholar]
  13. Quigley C. A., Friedman K. J., Johnson A., Lafreniere R. G., Silverman L. M., Lubahn D. B., Brown T. R., Wilson E. M., Willard H. F., French F. S. Complete deletion of the androgen receptor gene: definition of the null phenotype of the androgen insensitivity syndrome and determination of carrier status. J Clin Endocrinol Metab. 1992 Apr;74(4):927–933. doi: 10.1210/jcem.74.4.1347772. [DOI] [PubMed] [Google Scholar]
  14. Simental J. A., Sar M., Lane M. V., French F. S., Wilson E. M. Transcriptional activation and nuclear targeting signals of the human androgen receptor. J Biol Chem. 1991 Jan 5;266(1):510–518. [PubMed] [Google Scholar]
  15. Walker A. C., Stack E. M., Horsfall W. A. Familial male pseudohermaphroditism. Med J Aust. 1970 Jan 24;1(4):156–160. doi: 10.5694/j.1326-5377.1970.tb77782.x. [DOI] [PubMed] [Google Scholar]
  16. Wilson J. D., Harrod M. J., Goldstein J. L., Hemsell D. L., MacDonald P. C. Familial incomplete male pseudohermaphroditism, type 1. Evidence for androgen resistance and variable clinical manifestations in a family with the Reifenstein syndrome. N Engl J Med. 1974 May 16;290(20):1097–1103. doi: 10.1056/NEJM197405162902001. [DOI] [PubMed] [Google Scholar]

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