Human Genetics

, Volume 54, Issue 2, pp 133–143 | Cite as

X chromosome constitution and the human female phenotype

  • Eeva Therman
  • C. Denniston
  • Gloria E. Sarto
  • Margaret Ulber
Review Articles


The correlations of abnormal X chromosome constitutions and the resulting phenotypes in the human female are reviewed. The following hypotheses put forward to explain these correlations are discussed in detail: (1) The damage is done before X inactivation; (2) An effect is exerted between reactivation of the X chromosome(s) and meiosis in oocytes; (3) A recessive gene(s) in hemizygous condition might be expressed in the cases in which the same X is active in all cells; (4) A change in the number of presumed active regions on the inactive X chromosomes might have an effect; (5) A position effect, in that the region Xq13-q27 has to be intact in both X chromosomes to allow normal development, may be responsible; (6) An effect during the period when cells with different inactivation patterns compete is a probability; (7) The original X inactivation may be neither regular nor random.

The conclusion reached is that the phenotypic effects of a specific X chromosome aberration may be simultaneously exerted through different pathways (Tables 1 and 2). Hypotheses (2), (4), (5), and (6) are considered probable. Hypothesis (3) has been discarded, and there is very little evidence for hypotheses (1) and (7).


Internal Medicine Metabolic Disease Chromosome Aberration Phenotypic Effect Chromosome Constitution 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Allderdice, P. W., Miller, O. J., Miller, D. A., Klinger, H. P.: Spreading of inactivation in an (X;14) translocation. Am. J. Med. Genet. 2, 233–240 (1978)Google Scholar
  2. Barlow, P.: The influence of inactive chromosomes on human development. Humangenetik 17, 105–136 (1973)Google Scholar
  3. Bernstein, R., Wagner, J., Isdale, J., Nurse, G. T., Lane, A. B., Jenkins, T.: X-Y translocation in a retarded phenotypic male. J. Med. Genet. 15, 466–474 (1978)Google Scholar
  4. Bühler, E.: Clinical and cytological aspects of sex chromosome activity. Hereditas 86, 63–74 (1977)Google Scholar
  5. Campana, T., Szabo, P., Piomelli, S., Siniscalco, M.: The Xga antigen on red cells and fibroblasts. Cytogenet. Cell Genet. 22, 524–526 (1978)Google Scholar
  6. Cattanach, B. M.: Control of chromosome inactivation. Annu. Rev. Genet. 9, 1–18 (1975)Google Scholar
  7. Cohen, M. M., Lin, C.-C., Sybert, V., Orecchio, E. J.: Two human X-autosome translocations identified by autoradiography and fluorescence. Am. J. Hum. Genet. 24, 583–597 (1972)Google Scholar
  8. Daly, R. F., Patau, K., Therman, E., Sarto, G. E.: Structure and Barr body formation of an Xp+ chromosome with two inactivation centers. Am. J. Hum. Genet. 29, 83–93 (1977)Google Scholar
  9. Distèche, C., Hagemeijer, A., Frederic, J., Progneaux, D.: An abnormal large human chromosome identified as an end-to-end fusion of the two X's by combined results of the new banding techniques and microdensitometry. Clin. Genet. 3, 388–395 (1972)Google Scholar
  10. Eller, E., Frankenburg, W., Puck, M., Robinson, A.: Prognosis in newborn infants with X-chromosomal abnormalities. Pediatrics 47, 681–688 (1971)Google Scholar
  11. Engel, W., Vogel, W., Reinwein, H.: Autoradiographische Untersuchungen an einer X-Autosomentranslokation beim Menschen: 45,X,15-,tan(15qXq+)+. Cytogenetics 10, 87–98 (1971)Google Scholar
  12. Epstein, C. J., Smith, S., Travis, B., Tucker, G.: Both X chromosomes function before visible X-chromosome inactivation in female mouse embryos. Nature 274, 500–503 (1978)Google Scholar
  13. Fraccaro, M., maraschio, P., Pasquali, F., Scappaticci, S.: Women heterozygous for deficiency of the (p21→pter) region of the X chromosome are fertile. Hum. Genet. 39, 283–292 (1977)Google Scholar
  14. Garcia, J. E., Cummings, D. K., Wentz, A. C., Jones, H. W. Jr., Rary, J. M.: A 5/X chromosomal translocation in a patient with premature menopause. J. Hered. 68, 75–80 (1977)Google Scholar
  15. Gartler, S. M., Andina, R. J.: Mammalian X-chromosome inactivation. In: Advances in human genetics, Vol. 7. H. Harris, K. Hirschhorn (eds.), pp. 99–140. New York-London: Plenum Press 1976Google Scholar
  16. Gartler, S. M., Sparkes, R. S.: The Lyon-Beutler hypothesis and isochromosome X patients with the Turner syndrome. Lancet 1963 II, 411Google Scholar
  17. Gilgenkrantz, S., Mauuary, G., Dutrillaux, B., Masocco, G.: Translocation Xftosome et replication tardive. Humangenetik 26, 25–34 (1975)Google Scholar
  18. Grass, P. S., Schwartz, R. P., Deal, J., Parke, J. C. Jr.: Intra-X chromosome rearrangement, position effect and gonadal dysgenesis in an otherwise normal female. In: Program and Abstracts of the American Society of Human Genetics, 30th Annual Meeting, p. 95A. Chicago: University of Chicago Press 1979Google Scholar
  19. Grumbach, M. M.: Genetic mechanisms of sexual development. In: Genetic mechanisms of sexual development, H. L. Vallet, I. H. Porter (eds.) pp. 33–74. New York-San Francisco-London: Academic Press 1979Google Scholar
  20. Hagemeijer, A., Hoovers, J., Smit, E. M. E., Bootsma, D.: Replication pattern of the X chromosomes in three X/autosomal translocations. Cytogenet. Cell Genet. 18, 333–348 (1977)Google Scholar
  21. Hsu, S. H., Migeon, B. R., Bias, W. B.: Unreliability of the microcomplement fixation method for Xga typing of cultured fibroblasts. Cytogenet. Cell Genet. 16, 382–386 (1976)Google Scholar
  22. Johnson, V. P., Aceto, T. Jr., Likness, C.: Trisomy 14 mosaicism: Case report and review. Am. J. Med. Genet. 3, 331–339 (1979)Google Scholar
  23. Latt, S. A., Willard, H. F., Gerald, P. S.: BrdU-33258 Hoechst analysis of DNA replication in human lymphocytes with supernumerary or structurally abnormal X chromosomes. Chromosoma 57, 135–153 (1976)Google Scholar
  24. Luzzatto, L., Usanga, E. A., Bienzle, U., Esan, G. F. J., Fasuan, F. A.: Imbalance in X-chromosome expression: evidence for a human X-linked gene affecting growth of hemopoietic cells. Science 205, 1418–1420 (1979)Google Scholar
  25. Lyon, M. F.: Mechanisms and evolutionary origins of variable X-chromosome activity in mammals. Proc. Roy. Soc. Lond. B 187, 243–268 (1974)Google Scholar
  26. Maeda, T., Ohno, M., Takada, M., Nishida, M., Tsukioka, K., Tomita, H.: Turner's syndrome with a duplication-deficiency X chromosome derived from a maternal pericentric inversion X chromosome. Clin. Genet. 15, 259–266 (1979)Google Scholar
  27. Migeon, B. R.: X-chromosome inactivations as a determinant of female phenotype. In: Genetic mechanisms of sexual development, H. L. Vallet, I. H. Porter (eds.), pp. 293–303. New York-San Francisco-London: Academic Press 1979Google Scholar
  28. Migeon, B. R., Do, T. T.: In search of non-random X inactivation: Studies of fetal membranes heterozygous for glucose-6-phosphate dehydrogenase. Am. J. Hum. Genet. 31, 581–585 (1979)Google Scholar
  29. Mikkelsen, M.: Identification of active and inactive X chromosomes by BrdU incorporation and fluorochrome staining. In: Chromosomes today, Vol. 5, P. L. Pearson, K. R. Lewis (eds.), pp 409–414. New York: John Wiley & Sons 1976Google Scholar
  30. Mikkelsen, M., Dahl, G.: Unbalanced X/autosomal translocation with inactivation of the normal X chromosome. Cytogenet. Cell Genet. 12, 357–366 (1973)Google Scholar
  31. Mitelman, F., Levan, G.: Clustering of aberrations to specific chromosomes in human neoplasms. III. Incidence and geographic distribution of chromosome aberrations in 856 cases. Hereditas 89, 207–232 (1978)Google Scholar
  32. Niebuhr, E., Seemanová, E., Losan, F.: Familiární výskyt pericentrické inverze X chromosomu. Čs. Pediatr. 29, 245–247 (1974)Google Scholar
  33. Nikoliš, J., Stolević, E.: Recombinant chromosome as a result of pericentric inversions of X chromosome. Hum. Genet. 45, 115–122 (1978)Google Scholar
  34. Olanders, S.: Females with supernumerary X chromosomes. Stockholm-Gothenburg-Lund: Esselte Studium 1975Google Scholar
  35. Perez-Ballester, B., Greenblatt, R. B., Byrd, J. R.: Familial gonadal dysgenesis. Am. J. Obstet. Gynecol. 107, 1262–1263 (1970)Google Scholar
  36. Polani, P. E.: Chromosomal and other genetic influences on birth weight variation. In: Size at birth, pp. 127–164. Ciba Foundation Symposium 27 (new series). Amsterdam: ASP 1974Google Scholar
  37. Rapp, M., Therman, E., Denniston, C.: Nonpairing of the X and Y chromosomes in the spermatocytes of BDF1 mice. Cytogenet. Cell Genet. 19, 85–93 (1977)Google Scholar
  38. Riccardi, V. M.: Trisomy 8: An international study of 70 patients. Birth Defects 8 (3C), pp. 171–184 (1977)Google Scholar
  39. Ropers, H.-H., Wolff, G., Hitzeroth, H. W.: Preferential X inactivation in human placenta membranes: Is the paternal X inactive in early embryonic development of female manmals? Hum. Genet. 43, 265–273 (1978)Google Scholar
  40. Sarto, G. E., Therman, E.: Replication and inactivation of a dicentric X formed by telomeric fusion. Am. J. Obstet. Gynecol. (in press, 1980)Google Scholar
  41. Sarto, G. E., Therman, E., Patau, K.: X inactivation in man: A woman with t(Xq-;12q+). Am. J. Hum. Genet. 25, 262–270 (1973)Google Scholar
  42. Shapiro, L. J., Mohandas, T., Weiss, R., Romeo, G.: Noninactivation of an X-chromosome locus in man. Science 204, 1224–1226 (1979)Google Scholar
  43. Stengel-Rutkowski, S., Zankl, H., Rodewald, A., Sharrer, S., Chaudhuri, J. P., Zang, K. D.: Aspermia, associated with a presumably balanced X/autosomal translocation; karyotype 46,Y,t(X;5)(q28;q11). Hum. Genet. 31, 97–106 (1976)Google Scholar
  44. Summitt, R. L., Martens, P. R., Wilroy, R. S. Jr.: X-autosome translocation in normal mother and effectively 21-monosomic daughter. J. Pediatr. 84, 539–546 (1974)Google Scholar
  45. Summitt, R. L., Tipton, R. E., Wilroy, R. S. Jr., Martens, P. R., Phelan, J. P.: X-autosome translocations: a review. Birth Defects 14 (6C), 219–247 (1978)Google Scholar
  46. Takagi, N., Sasaki, M.: Preferential inactivation of the paternally derived X chromosome in extraembryonic membranes of the mouse. Nature 256, 640–642 (1975)Google Scholar
  47. Takagi, N., Wake, N., Sasaki, M.: Cytological evidence for preferential inactivation of the paternally derived X chromosome in XX mouse blastocytes. Cytogenet. Cell Genet. 20, 240–248 (1978)Google Scholar
  48. Thelen, T. H., Abrams, D. J., Fisch, R. O.: Multiple abnormalities due to possible genetic inactivation in an X/autosomal translocation. Am. J. Hum. Genet. 23, 410–418 (1971)Google Scholar
  49. Therman, E., Patau, K.: Abnormal X chromosomes in man: Origin, behavior and effects. Humangenetik 25, 1–16 (1974)Google Scholar
  50. Therman, E., Sarto, G. E., Distèche, C., Denniston, C.: A possible active segment on the inactive human X chromosome. Chromosoma 59, 137–145 (1976)Google Scholar
  51. Therman, E., Sarto, G. E., Palmer, C. G., Kallio, H., Denniston, C.: Position of the human X inactivation center on Xq. Hum. Genet. 50, 59–64 (1979)Google Scholar
  52. Tiepolo, L., Zuffardi, O., Rodewald, A.: Nullisomy for the distal portion of Xp in a male child with a X/Y translocation. Hum. Genet. 39, 277–281 (1977)Google Scholar
  53. Wake, N., Takagi, N., Sasaki, M.: Non-random inactivation of X chromosome in the rat yolk sac. Nature 262, 580–581 (1976)Google Scholar
  54. Willard, H. F., Latt, S. A.: Analysis of deoxyribonucleic acid replication in human X chromosomes by fluorescence microscopy. Am. J. Hum. Genet. 28, 213–227 (1976)Google Scholar
  55. Yamada, Y., Neriishi, S.: Penta X (49,XXXXX) chromosome constitution. Jpn. J. Hum. Genet. 16, 15–21 (1971)Google Scholar
  56. Zabel, B. U., Baumann, W. A., Pirntke, W., Gerhard-Ratschow, K.: X-inactivation pattern in three cases of X/autosome translocation. Am. J. Med. Genet. 1, 309–317 (1978)Google Scholar
  57. Zuffardi, O., Tiepolo, L., Scappaticci, S., Francesconi, D., Bianchi, C., Natale, D. di: Reduced phenotypic effect of partial trisomy 1q in a X/1 translocation. Ann. Genet. 20, 191–194 (1977)Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • Eeva Therman
    • 1
  • C. Denniston
    • 1
  • Gloria E. Sarto
    • 2
  • Margaret Ulber
    • 1
  1. 1.Department of Medical GeneticsUniversity of WisconsinMadisonUSA
  2. 2.Department of Obstetrics and GynecologyNorthwestern UniversityChicagoUSA

Personalised recommendations