Genetics of intersexuality

Journal of Gay and Lesbian Psychotherapy

Volumn 10, Issue 2, 2006, Pages 9-26

  Vilain, Eric ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Ambiguous genitalia; Endocrinology; Gender; Gender assignment; Gender determination; Genetics; Hermaphroditism; Intersex; Intersexuality; Sex determination; Sex differentiation; Sexual dimorphism

Indexed keywords

EID: 33746578403     PISSN: 08917140     EISSN: 15407128     Source Type: Journal    
DOI: 10.1300/J236v10n02_02     Document Type: Article

References (54)

1. Affara, N.A., Chalmers, I.J. & Ferguson-Smith, M.A. (1993), Analysis of the SRY gene in 22 sex-reversed XY females identifies four new point mutations in the conserved DNA binding domain. Human Molecular Genetics, 2:785-789.
2. Arnold, A.P. (1996), Genetically triggered sexual differentiation of brain and behavior. Hormones & Behavior, 30:495-505.
3. Arnold, A.P. & Gorski, R.A. (1984), Gonadal steroid induction of structural sex differences in the central nervous system. Annual Review Neuroscience, 7:413-442.
4. Berta, P., Hawkins, J.R., Sinclair, A., Taylor, A. Griffiths, B.L., Goodfellow, P.N. & Fellous, M. (1990), Genetic evidence equating SRY and the testis-determining factor. Nature, 349:448-450.
5. Beyer, C., Eusterschulte, B., Pilgrim, C. & Reisert, I. (1992a), Sex steroids do not alter sex differences in tyrosine hydroxylase activity of dopaminergic neurons in vitro. Cell & Tissue Research, 270:547-552.
6. Beyer, C., Kolbinger, W., Froehlich, U., Pilgrim, C. & Reisert, I. (1992b), Sex differences of hypothalamic prolactin cells develop independently of the presence of sex steroids. Brain Research, 593:253-256.
7. Beyer, C., Pilgrim, C. & Reisert, I. (1991), Dopamine content and metabolism in mesencephalic and diencephalic cell cultures: Sex differences and effects of sex steroids. J. Neuroscience, 11:1325-1333.
8. Brown, S., Yu, C., Lanzano, P., Heller, D., Thomas, L., Warburton, D., Kitajewski, J. & Stadtmauer, L. (1998), A de novo mutation (Gln2Stop at the 5′ end of the SRY gene leads to sex reversal with partial ovarian function. American J. Human Genetics, 62:189-192.
9. Carruth, L.L., Reisert, I. & Arnold, A.P. (2002), Sex chromosome genes directly affect brain sexual differentiation. Nature Neuroscience, 5:933-934.
10. Clépet, C., Schafer, A.J., Sinclair, A.H., Palmer, M.S., Lovell-Badge, R. & Goodfellow, P.N. (1993), The human SRY transcript. Human Molecular Genetics, 2:2007-2012.
11. Dewing, P., Chiang, C.W., Sinchak, K., Sim, H., Fernagut, P.O., Kelly, S., Chesselet, M.F., Micevych, P.E., Albrecht, K.H., Harley, V.R. & Vilain, E. (2006), Direct regulation of adult brain function by the male-specific factor SRY. Current Biology, 16:415-420.
12. Dewing, P., Shi, T., Horvath, S. & Vilain, E. (2003), Sexually dimorphic gene expression in mouse brain precedes gonadal differentiation. Molecular Brain Research, 118:82-90.
13. Domenice, S., Yumie Nishi, M., Correia Billerbeck, A.E., Latronico, A.C., Aparecida Medeiros, M., Russell, A.J., Vass, K., Marino Carvalho, F., Costa Frade, E.M., Prado Arnhold, I.J. & Bilharinho Mendonca, B. (1998), A novel missense mutation (S18N) in the 5′ non-HMG box region of the SRY gene in a patient with partial gonadal dysgenesis and his normal male relatives. Human Genetics, 102:213-215.
14. Dreger, A.D., Chase, C., Sousa, A. & Frader, J. (2005), Changing the nomenclature/taxonomy for intersex: A scientific and clinical rationale. J. Pediatric Endocrinology and Metabolism, 18:729-733.
15. EUROCAT Working Group (1997), Eurocat report 7. Fifteen years of surveillance of congenital anomalies in Europe 1980-1994. Scientific Institute of Public Health-Louis Pasteur, Brussels.
16. Ford C.E., Jones, K.W., Polani, P.E., de Almeida, J.C. & Brigg, J.H. (1959), A sex chromosome anomaly in a case of gonadal dysgenesis (Turner Syndrome). Lancet, 1:711-713.
17. Forest, M.G., David, M. & Morel, Y. (1993), Prenatal diagnosis and treatment of 21-hydroxylase deficiency. J. Steroid Biochemistry & Molecular Biology, 45:75-82.
18. Goldschmidt, R. (1917), Intersexuality and the endocrine aspect of sex. Endocrinology, 1:453-456.
19. Gorski, R. (1991), Sexual differentiation of the endocrine brain and its control. In: Brain Endocrinology (2nd edition), ed. M. Mona. New York: Raven Press, pp. 71-104.
20. Green, R. (2000), Family cooccurrence of "gender dysphoria": Ten siblings or parent-child pairs. Archives Sexual Behavior, 29(5):499-507.
21. Grumbach, M.M. & Conte, F.A. (1998), Disorders of sex differentiation. In: Williams Textbook of Endocrinology (9th edition), eds. J.D. Wilson, D.W. Foster, H.M. Kronenberg & P.R. Larsen. Philadelphia: W B Saunders, pp. 1303-1425.
22. Guo, W., Burris, T.P. & McCabe, E.R.B. (1995), Expression of DAX-1, the gene responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism, in the hypothalamic-pituitary-adrenal/ gonadal axis. Biochemical & Molecular Medicine, 56:8-13.
23. Harry, J.L., Koopman, P., Brennan, F.E., Graves, J.A. & Renfree, M.B. (1995), Widespread expression of the testis-determining gene SRY in a marsupial. Nature Genetics, 11:347-349.
24. Hawkins, J.R., Taylor, A., Berta, P., Levillieers, J. Van der Auwera, B. & Goodfellow, P.N. (1992), Mutational analysis of SRY: Nonsense and missense mutations in XY sex reversal. Human Genetics, 88:471-474.
25. Hawkins, J.R., Taylor, A., Goodfellow, P.N., Migeon, C.J., Smith, K.D. & Berkovitz, G.D. (1992), Evidence for increased prevalence of SRY mutations in XY females with complete rather than partial gonadal dysgenesis. American J. Human Genetics, 51:979-984.
26. Hughes, I.A., Houk, C., Ahmed, S.F., Lee, P.A. & the LWPES/ESPE Consensus Group. (in press), "Consensus statement on management of intersex disorders" Archives of Disease in Childhood.
27. Jacobs, P.A. & Strong, J.A. (1959), A case of human intersexuality having possible XXY sex-determining mechanism. Nature, 183:302-303.
28. Jäger, R.J., Anvret, M., Hall, K. & Scherer, G. (1990), A human XY female with frame shift mutation in the candidate sex determining gene, SRY. Nature, 348:452-454.
29. Jost, A. (1947), Recherches sur la différenciation sexuelle de l'embryon de lapin. III. Rôle des gonads fœtales dans la différenciation sexuelle somatique [Research on sexual differentiation of rabbit embryos]. Arch. d'anatomie et de microscopie morphologique expérimentale, 36:271-315.
30. Jost, A. (1970), Hormonal factors in the sex differentiation of the mammalian foetus. Philosophical Transactions of the Royal Society. London, B: Biological Sciences, 259:119-130.
31. Jost, A. Vigier, B., Prepin, J. & Perchellet, J.P. (1973), Studies on sex differentiation in mammals. Recent Progress in Hormonal Research, 29:1-41.
32. Kaleva, M., Virtanen, H., Haavisto, A.M., Main, K., Skakkebaek, N.E. & Toppari, J. (2001), Incidence of cryptorchidism in Finnish Boys. Hormone Research, 55:54.
33. Kawata, M. (1995), Roles of steroid hormones and their receptors in structural organization in the nervous system. Neuroscience Research, 24:1-46.
34. Koopman, P., Munserberg, A., Capel, B., Vivian, N. & Lovell-Badge, R. (1990), Expression of a candidate sex-determining gene during mouse testis differentiation. Nature, 348:450-452.
35. Lahr, G., Maxson, S.C., Mayer, A., Just, W., Pilgrim, C. & Reisert, I. (1995), Transcription of the Y chromosomal gene, Sry, in adult mouse brain. Molecular Brain Research, 33:179-182, 1995.
36. MacLusky, N.J. & Naftolin, F. (1981), Sexual differentiation of the central nervous system. Science, 211:1294-1303.
37. McElreavey, K., Rappaport, R., Vilain, E., Abbas, N., Richaud, F., Lortat-Jacob, S., Berger R., Le Coniat, M., Boucekkine, C. & Kucheria K. (1992), A rninority of 46,XX true hermaphrodites are positive for the Y-DNA sequence including SRY. Human Genetics, 90(1-2):121-125.
38. McElreavey, K., Vilain, E., Abbas, N., Costa, J.M., Souleyreau, N., Kucheria, K., Boucekkine, C., Thibaud, E., Brauner, R., Flamant, F. & Fellous, M. (1992), XY sex-reversal associated with a deletion 5′ to the SRY HMG-box in the testis-determining-region. Proceedings of the National Academy of Sciences USA, 89:11016-11020.
39. McElreavey, K., Vilain, E., Boucekkine, C., Vidaud, M., Jaubert, F., Richaud, F. & Fellous, M. (1992), XY sex reversal associated with a nonsense mutation in SRY. Genomics, 13:838-840.
40. McEwen, B.S. (1981), Neural gonadal steroid actions. Science, 211:1303-1311.
41. Müller, J., Schwartz, M. & Skakkebaek, N.E., (1992), Analysis of the sex determining region of the Y chromosome (SRY) in sex reversed patients: Point mutation in SRY causing sex reversion in a 46, XY female. J. Clinical Endocrinology & Metabolism, 75:331-33.
42. Palmer, M.S., Sinclair, A.H., Berta, P., Ellis, N.A., Goodfellow, P.N., Abbas, N.E. & Fellous, M. (1989), Genetic evidence that ZFY is not the testis-determining factor. Nature, 342:937-939.
43. Phoenix, C.H., Goy, R.W., Gerall, A.A. & Young, W.C. (1959), Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology, 65:396-382.
44. Pierik, F.H., Burdof, A., Nijman, J.M.R., de Muinck Keizer-Schrama, S.M.P.F., Juttmann, R.E. & Weber, R.F.A. (2002), A high hypospadias rate in The Netherlands. Human Reproduction, 17(4):1112-1115.
45. Poulat, F., Soullier, S., Goze, C., Heitz, F., Calas, B. & Berta, P. (1994), Description and functional implications of a novel mutation in the sex-determining gene SRY. Human Mutation, 3:200-204.
46. Sinclair, A.H., Berta, P., Palmer, M.S., Hawkins, J.R., Griffiths, B.L., Smith, M.J., Foster, J.W., Frischauf, A.M., Lovell-Badge, R. & Goodfellow, P.N. (1990), A gene from the human sex-determining region encodes a protein with homology to a conserved DNA binding motif. Nature, 346:240-244.
47. Tajima, J., Nakae, J., Shinohara, N. & Fujieda, K. (1994), A novel mutation localized in the 3′ non-HMG box region of the SRY gene in 46, XY gonadal dysgenesis. Human Molecular Genetics, 3:1187-1189.
48. Teixeira, J. Maheswaran, S. & Donahoe, P.K. (2001), Müllerian Inhibiting Substance: An instructive developmental hormone with diagnostic and possible therapeutic applications. Endocrine Reviews, 22(5):657-674.
49. Vilain, E. & McCabe, E.R.B. (1998), Mammalian sex determination: From gonads to brain. Molecular Genetics and Metabolism, 65:74-84.
50. Vilain, E., McElreavey, K.D., Jaubert, F., Raymond, J-P., Richaud, F. & Fellous, M. (1992), Familial case with sequence variant in the testis-determining region associated with two sex phenotypes. American J. Human Genetics, 50:1008-1011.
51. Wade, J. & Arnold, A.P. (1992), Functional testicular tissue does not masculinize development of the zebra finch song system. Proceedings of the National Academy of Sciences USA, 93:5264-5268.
52. Wade, J., Gong, A. & Arnold, A.P. (1997), Effects of embryonic estrogen on differentiation of the gonads and secondary sexual characteristics of male zebra finches. J. Experimental Zoology, 278:405-411.
53. Xavier, M. [Edward Irenaeus Prime-Stevenson] (1975), The Intersexes: A History of Similisexualism as a Problem in Social Life. New York: Arno Press.
54. Zeng, Y.T., Ren, Z.R., Zhang, M.L., Huang, Y., Zeng, F.Y. & Huang, S.Z. (1993), A new de novo mutation (A113T) in HMG box of the SRY gene leads to XY gonadal dysgenesis. J. Medical Genetics, 30:655-657.