Journal of Clinical Immunology

, Volume 12, Issue 2, pp 139–143 | Cite as

Females with a disorder phenotypically identical to X-linked agammaglobulinemia

  • Mary Ellen Conley
  • Sharon K. Sweinberg
Original Articles
Accepted:

Abstract

Clinical and laboratory findings in two girls with a disorder phenotypically indistinguishable from typical X-linked agammaglobulinemia (XLA) are described. To examine the possibility that subtle defects in the X chromosome might explain the findings, detailed genetic studies were performed on one of these patients. Cytogenetic studies showed a normal 46XX karyotype. Southern blot analysis of her DNA showed that she had inherited a maternal and a paternal allele at sites flanking the locus for typical XLA at Xq22, making a microdeletion or uniparental disomy unlikely. To determine whether both of her X chromosomes could function as the active X, somatic-cell hybrids that selectively retained the active X were produced from her activated T cells. A normal random pattern of X inactivation was seen. Of 21 T-cell hybrids, 3 retained both X chromosomes, 7 had one X as the active X, and 11 had the other X as the active X. We have interpreted these studies as indicating that there is an autosomal recessive disorder that is phenotypically identical to XLA.

Key words

B cells immunodeficiencies X chromosome X-linked agammaglobulinemia hypogammaglobulinemia 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Conley ME, Brown P, Pickard AR, Buckley RH, Miller DS, Raskind WH, Singer JW, Fialkow PJ: Expression of the gene defect in X-linked agammaglobulinemia. N Engl J Med 315:564–567, 1986Google Scholar
  2. 2.
    Fearon ER, Winkelstein JA, Civin CI, Pardoll DM, Vogelstein B: Carrier detection in X-linked agammaglobulinemia by analysis of X-chromosome inactivation. N Engl J Med 316:427–431, 1987Google Scholar
  3. 3.
    Conley ME, Puck, JM: Carrier detection in typical and atypical X-linked agammaglobulinemia. J Pediat 112:688–694, 1988Google Scholar
  4. 4.
    Hendriks RW, Mensink EJBM, Kraakman MEM, Thompson A, Schuurman RKB: Evidence for male X chromosomal mosaicism in X-linked agammaglobulinemia. Hum Genet 83:267–270, 1989Google Scholar
  5. 5.
    Repine JE, Clawson CC, White JG, Holmes B: Spectrum of function of neutrophils from carriers of sex-linked chronic granulomatous disease. J Pediat 87:901–907, 1975Google Scholar
  6. 6.
    Nisen PD, Waber PG: Nonrandom X chromosome DNA methylation patterns in hemophiliac females. J Clin Invest 83:1400–1403, 1989Google Scholar
  7. 7.
    Fasth A: Primary immunodeficiency disorders in Sweden: Cases among children, 1974–1979. J Clin Immunol 2:86–92, 1982Google Scholar
  8. 8.
    Verellen-Dumoulin C, Freund M, De Meyer R, Laterre C, Frederic J, Thompson MW, Markovic VD, Worton RG: Expression of an X-linked muscular dystrophy in a female due to translocation involving Xp21 and non-random inactivation of the normal X chromosome. Hum Genet 67:115–119, 1984Google Scholar
  9. 9.
    Merry DE, Lesko JG, Siu V, Flintoff, WF, Collins F, Lewis RA, Nussbaum RL: DXS165 detects a translocation breakpoint in a woman with choroideremia and a de Novo X; 13 translocation. Genomics 6:609–615, 1990Google Scholar
  10. 10.
    Therman E, Patau D: Abnormal X chromosomes in Man. Origin, behavior and effects. Hum Genet 25:1–16, 1974Google Scholar
  11. 11.
    Voss R, Ben-Simon E, Avital A, Godfrey S, Zlotogora J, Dagan J, Tikochinski Y, Hillel J: Isodisomy of chromosome 7 in a patient with cystic fibrosis: Could uniparental disomy be common in humans? Am J Hum Genet 45:373–380, 1989Google Scholar
  12. 12.
    Spence JE, Perciaccante RG, Greig GM, Willard HF, Ledbetter DH, Hejtmancik JF, Pollack MS, O'Brien WE, Baudet AL: Uniparental disomy as a mechanism for human genetic disease. Am J Hum Genet 42:217–226, 1988Google Scholar
  13. 13.
    Conley ME: B cells in patients with X-linked agammaglobulinemia. J Immunol 134:3070–3074, 1985Google Scholar
  14. 14.
    Conley ME, Lavoie A, Briggs C, Brown P, Guerra C, Puck JM: Nonrandom X chromosome inactivation in B cells from carriers of X chromosome-linked severe combined immunodeficiency. Proc Natl Acad Sci 85:3090–3094, 1988Google Scholar
  15. 15.
    Conley ME, Puck JM: Definition of the gene loci in X-linked immunodeficiencies. Immunol Invest 17:425–463, 1988Google Scholar
  16. 16.
    Puck JM, Nussbaum RL, Conley ME: Carrier detection in X-linked severe combined immunodeficiency based on patterns of X chromosome inactivation. J Clin Invest 79:1395–1400, 1987Google Scholar
  17. 17.
    Kidd KK, Bowcock AM, Schmidtke J, Track RK, Ricciuti F, Hutchings G, Bale A, Pearson P, Willard HF: Report of the DNA committee and catalogs of cloned and mapped genes and DNA polymorphisms. Cytogenet Cell Genet 51:622–947, 1989Google Scholar
  18. 18.
    Guioli S, Arveiler B, Bardoni B, Notarangelo LD, Panina P, Duse M, Ugazio A, Oberle I, de Saint Basile G, Mandel JL, Camerino G: Close linkage of probe p212 (DXS178) to X-linked agammaglobulinemia. Hum Genet 84:19–21, 1989Google Scholar
  19. 19.
    Kwan SP, Terwilliger J, Parmley R, Raghu G, Sandkuyl LA, Ott J, Ochs H, Wedgwood R, Rosen F: Identification of a closely linked DNA marker, DXS178, to further refine the X-linked agammaglobulinemia locus. Genomics 6:238–242, 1990Google Scholar
  20. 20.
    WHO: Report of a WHO sponsored meeting. Primary immunodeficiency diseases. Immunodefic Rev 1:173–205, 1989Google Scholar
  21. 21.
    Ochs HD, Wedgwood RJ: Disorders of the B-cell system.In Immunologic Disorders in Infants and Children, ER Stiehm (ed). Philadelphia, W. B. Saunders, 1989, pp 226–236Google Scholar
  22. 22.
    Lederman HM, Winkelstein JA: X-linked agammaglobulinemia: An analysis of 96 patients. Medicine 64:145–156, 1985Google Scholar
  23. 23.
    Aiuti F, Fontana L, Gatti RA: Membrane-bound immunoglobulin (Ig) and in vitro production of Ig by lymphoid cells from patients with primary immunodeficiencies. Scand J Immunol 2:9–16, 1973Google Scholar
  24. 24.
    Hoffman T, Winchester R, Schulkind M, Frias JL, Ayoub EM, Good RA: Hypoimmunoglobulinemia with normal T cell function in female siblings. Clin Immunol Immunopathol 7:364–371, 1977Google Scholar
  25. 25.
    McKinney RE Jr, Katz SL, Wilfert CM: Chronic enteroviral meningoencephalitis in agammaglobulinemic patients. Rev Infect Dis 9:334–356, 1987Google Scholar

Copyright information

© Plenum Publishing Corporation 1992

Authors and Affiliations

  • Mary Ellen Conley
    • 1
  • Sharon K. Sweinberg
    • 2
  1. 1.University of Tennessee College of Medicine and St. Jude Children's Research HospitalMemphis
  2. 2.Children's Hospital of PhiladelphiaPhiladelphia

Personalised recommendations