Summary
Two 46,XY females with tandem duplications of an X short arm segment were studied by cytogenetic and Southern blot analysis. The results show that the duplicated segment in each case included the Xp21.2–Xp22.2 interval, resulting in a double dose of ZFX on the single active X chromosome. The results from our two cases, in conjunction with those reported by other workers, lead us to conclude that the duplication is the reason for the sex inversion. If ZFY and ZFX are indeed sex-determining gene loci, these findings favour a model of sex determination characterized by antagonistic interaction between these genes.
References
Affara NA, Ferguson-Smith MA, Magenis RE, Tolmie JL, Boyd E, Cooke A, Jamieson D, Kwok K, Mitchell M, Snadden L (1987) Mapping the testis determinants by an analysis of Y-specific sequences in males with apparent XX and XO karyotypes and females with XY karyotypes. Nucleic Acids Res 15:7325–7342
Bernstein R, Jenkins T, Dawson B, Wagner J, Dewald G, Koo GC, Wachtel SS (1980) Female phenotype and multiple abnormalities in sibs with a Y chromosome and partial X chromosome duplication: H-Y antigen and Xg blood group findings. J Med Genet 17: 291–300
Disteche CM, Casanova M, Saal H, Friedman C, Sybert V, Graham J, Thuline H, Page DC, Fellous M (1986) Small deletions of the short arm of the Y chromosome in 46,XY females. Proc Natl Acad Sci USA 83:7841–7844
German J (1988) Gonadal dimorphism explained as a dosage effect of a locus on the sex chromosomes, the gonad-differentiation locus. Am J Hum Genet 42:414–421
ISCN (1985) An international system for human cytogenetic nomenclature. Harnden DG, Klinger HP (eds), Published in collaboration with Cytogenet Cell Genet. Karger, Basel
Miyada CG, Wallace RB (1987) Oligonucleotide hybridization techniques. Methods Enzymol 154:94–107
Müller G, Schempp W (1989) Mapping the human ZFX locus to Xp21.3 by in situ hybridization. Hum Genet 82 (in press)
Müller U, Donlon T, Schmid M, Fitch N, Richer C-L, Lalande M, Latt SA (1986) Deletion mapping of the testis determining locus with DNA probes in 46,XX males and in 46,XY and 46,X,dic(Y) females. Nucleic Acids Res 14:6489–6505
Natt E, Westphal E-M, Toth-Fejel SE, Magenis RE, Buist NRM, Rettenmeier R, Scherer G (1987) Inherited and de novo deletion of the tyrosine aminotransferase gene locus at 16q22.1–q22.3 in a patient with tyrosinemia type II. Hum Genet 77:352–358
Page DC (1988) Is ZFY the sex-determining gene on the human Y chromosome? Philos Trans R Soc Lond [Biol] (in press)
Page DC, Mosher R, Simpson EM, Fisher EMC, Mardon G, Pollack J, McGillivray B, Chapelle A de la, Brown LG (1987) The sex-determining region of the human Y chromosome encodes a finger protein. Cell 51:1091–1104
Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chainterminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467
Schempp W, Meer B (1983) Cytologic evidence for three human X chromosomal segments escaping inactivation. Hum Genet 63: 171–174
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Scherer, G., Schempp, W., Baccichetti, C. et al. Duplication of an Xp segment that includes the ZFX locus causes sex inversion in man. Hum Genet 81, 291–294 (1989). https://doi.org/10.1007/BF00279008
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00279008