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Human Genetics

, Volume 92, Issue 6, pp 571–576 | Cite as

Familial true hermaphroditism: paternal and maternal transmission of true hermaphroditism (46,XX) and XX maleness in the absence of Y-chromosomal sequences

  • U. Kuhnle
  • H. P. Schwarz
  • U. Löhrs
  • S. Stengel-Ruthkowski
  • H. Cleve
  • A. Braun
Original Investigations

Abstract

We report on 46,XX true hermaphroditism and 46,XX maleness coexisting in the same pedigree, with maternal as well as paternal transmission of the disorder. Molecular genetic analysis showed that both hermaphrodites as well as the 46,XX male were negative for Y-chromosomal sequences. Thus, this pedigree is highly informative and allows the following conclusions: first, the maternal as well as paternal transmission of the disorder allows the possibility of an autosomal dominant as well as an X-chromosomal dominant mode of inheritance; second, testicular determination in the absence of Y-specific sequences in familial 46,XX true hermaphrodites as well as in 46,XX males seems to be due to the varying expression of the same genetic defect; and third, there is incomplete penetrance of the defect.

Keywords

Internal Medicine Genetic Analysis Metabolic Disease Genetic Defect Dominant Mode 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Aaronson IA (1985) True hermaphroditism. A review of 41 cases with observations on testicular histology and function. Br J Urol 57:775–779Google Scholar
  2. Abbas NE, Toublanc JE, Boucekkine C, Toublanc M, Affara NA, Job J-C, Fellous M (1990) A possible common origin of ‘Y-negative’ human XX-males and XX true hermaphrodites. Hum Genet 84:356–360Google Scholar
  3. Affara NA (1991) Sex and the single Y. Bio Essays 13:475–478Google Scholar
  4. Berkovitz GD, Fechner PY, Marcantonio SM, Bland G, Stetten G, Goodfellow PN, Smith KB, Migeon CJ (1992) The role of the sex-determining region of the Y chromosome (SRY) in the etiology of 46,XX true hermaphroditism. Hum Genet 88:411–416Google Scholar
  5. Berta Ph, Hawkins JR, Sinclair AH, Taylor A, Griffiths BL, Goodfellow PN, Fellous M (1990) Genetic evidence equating SRY and the testis-determing factor. Nature 348:448–450Google Scholar
  6. Bowry RB, Honore LH, Johnson HW, Kliman MR, Marshall RH (1981) Familial true hermaphroditism: the intersex child. Pediatr Adolesc Endocrinol 8:105–110Google Scholar
  7. Braun A, Kammerer S, Cleve H, Löhrs U, Schwarz HP, Kuhnle U (1993) True hermaphroditism in a 46,XY individual caused by a postzygotic somatic point mutation in the male gonadal sex-determining locus (SRY). Molecular genetics and histological findings in a sporadic case. Am J Hum Genet 52:578–585Google Scholar
  8. Chapelle A de la (1987) The Y-chromosomal and autosomal testisdetermining genes. Development [Suppl] 101:33–38Google Scholar
  9. Damiani D, Billerbeck AEC, Goldberg ACK, Setian N, Fellous M, Kalil J (1990) Investigation of the ZFY gene in XX true hermaphroditism and Swyer syndrome. Hum Genet 85:85–88Google Scholar
  10. Ellis NA, Goodfellow PJ, Pym B, Smith M, Palmer M, Frischauf A-M, Goodfellow PN (1989) The pseudoautosomal boundary in man is defined by an ALU repeat sequence inserted on the Y chromosome. Nature 337:81–84Google Scholar
  11. Fraccaro M, Tiepolo L, Zuffardi O, Chiumello G, Di Natale B, Gargantini L, Wolf U (1979) Familial XX true hermaphroditism and the H-Y antigen. Hum Genet 48:45–52Google Scholar
  12. Harley VR, Jackson DI, Hextall J, Hawkins JR, Berkovitz GD, Sockanathan S, Lovell-Badge R, Goodfellow PN (1992) DNA binding activity of recombinant SRY from normal males and XY females. Science 255:453–456Google Scholar
  13. Jäger RJ, Anvret M, Hall K, Scherer G (1990) A human XY female with a frame shift mutation in the candidate testis-determining gene SRY. Nature 348:452–454Google Scholar
  14. Knorr D, Beckmann D, Bidlingmaier F, Helmig F-J, Sippell WG (1979) Plasma testosterone in male puberty. II. hCG stimulation test in boys with hypospadia. Acta Endocrinol (Copenh) 90:365–371Google Scholar
  15. Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R (1991) Male development of chromosomally female mice transgenic for SRY. Nature 351:117–121Google Scholar
  16. Milner WA, Garlick WB, Fink AJ, Stein AA (1958) True hermaphrodite siblings. J Urol 79:1003–1007Google Scholar
  17. Mori Y, Mizutani S (1968) Familial hermaphroditism in genetic females. Jpn J Urol 59:857–861Google Scholar
  18. Niekerk WA van (1981) True hermaphroditism. In: Josso N (ed) The intersex child. Karger, Basel, pp 80–99Google Scholar
  19. Niekerk WA van, Retief AE (1981) The gonads of human true hermaphrodites. Hum Genet 58:117–122Google Scholar
  20. Ostrer H, Wright G, Clayton M, Skordis N, MacGillivray MH (1989) Familial XX chromosomal maleness does not arise from a Y chromosomal translocation. J Pediatr 114:977–982Google Scholar
  21. Palmer MS, Sinclair AH, Berta P, Ellis NA, Goodfellow PN, Abbas NE, Fellous M (1989) Genetic evidence that ZFY is not the testis-determining factor. Nature 342:937–939Google Scholar
  22. Pereira ET, Almeida JCC de, Gunha A, Patton M, Taylor R, Jeffrey S (1991) Use of probes for ZFY, SRY, and the Y pseudoautosomal boundary in XX males, XX true hermaphrodites, and an XY female. J Med Genet 28:591–595Google Scholar
  23. Ramsay M, Bernstein R, Zwane E, Page DC, Jenkins T (1988) XX true hermaphroditism in Southern African Blacks: An enigma of primary sexual differentiation. Am J Hum Genet 43:4–13Google Scholar
  24. Rosenberg HS, Clayton GW, Hsu TC (1963) Familial true hermaphrodism. J Clin Endocrinol Metab 23:203–206Google Scholar
  25. Schnackenburg K von, Bidlingmaier F, Knorr D (1980) 17-hydroxy-progesterone, androstendione and testosterone in normal children and in prepubertal patients with congenital adrenalhyperplasia. Eur J Pediatr 133:259–267Google Scholar
  26. Schneider-Gädicke A, Beer-Romero P, Brown LG, Nussbaum R, Page DC (1989) ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation. Cell 57:1247–1258Google Scholar
  27. Sinclair AH, Berta Ph, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, Foster JW, Frischauf A-M, Lovell-Badge R, Goodfellow PN (1990) A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346:240–244Google Scholar
  28. Skordis NA, Stetka DG, MacGillivray MH, Greenfield SP (1987) Familial 46,XX males coexisting with familial 46,XX true hermaphrodites in the same pedigree. J Pediatr 110:244–248Google Scholar
  29. Tazaki H, Ikeda N, Omori S (1964) True hermaphrodites in Japan. Report of a case and review of the literature. Keio J Med 13:143–154Google Scholar
  30. Vergnaud G, Page DC, Simmler MC, Brown L, Rouyer F, Noel B, Botstein D, Chapelle A de la, Weissenbach J (1986) A deletion map of the human Y chromosome based on DNA hybridizaion. Am J Hum Genet 38:109–124Google Scholar
  31. Waibel F, Scherer G, Fraccaro M, Hustinx TWJ, Weissenbach J, Wieland J, Mayerova A, Back E, Wolf U (1987) Absence of Y-specific DNA sequences in human 46,XX true hermaphrodites and in 45,X mixed gonadal dysgenesis. Hum Genet 76:332–336Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • U. Kuhnle
    • 1
  • H. P. Schwarz
    • 1
  • U. Löhrs
    • 3
  • S. Stengel-Ruthkowski
    • 4
  • H. Cleve
    • 2
  • A. Braun
    • 1
    • 2
  1. 1.Universitäts-KinderklinikMünchenGermany
  2. 2.Institut für Anthropologie und Humangenetik der UniversitätMünchenGermany
  3. 3.Institut für Pathologie der UniversitätMünchenGermany
  4. 4.Kinderzentrum MünchenMünchenGermany

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