Skip to main content

Advertisement

SpringerLink
Log in

The molecular basis of X-linked immunodeficiency disease

  • The X Chromosome
  • Published:
Journal of Inherited Metabolic Disease

Summary

The molecular bases of the X-linked immunodeficiency diseases remain largely undetermined. Two of the genes involved in these diseases have been isolated, namely the genes for X-linked chronic granulomatous disease and properdin deficiency, and substantial progress has now been made in identifying the genes which are defective in the other five diseases, Wiskott-Aldrich syndrome, X-linked severe combined immunodeficiency, X-linked agammaglobulinaemia, X-linked hyper-IgM and X-linked lymphoproliferative syndrome. We review here the nature of the diseases, progress made in identifying and isolating the genes involved and the prospects for improved prenatal detection, carrier status determination and treatment of these life-threatening conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Conley ME, Sullivan JL, Neidich JA, Puck JM (1990) X Chromosome inactivation patterns in obligate carriers of X-linked lymphoproliferative syndrome.Clin Immunol Immunopathol 55: 486–491.

    Google Scholar 

  • de Saint Basile G, Arveiler B, Oberle I et al (1987) Close linkage of the locus for X chromosome-linked severe combined immunodeficiency to polymorphic DNA markers in Xq11–q13.Proc Natl Acad Sci USA 84: 7576–7579.

    Google Scholar 

  • Francke U, Ochs HD, Darras BT, Swaroop A (1990) Origin of mutations in two families with X-linked chronic granulomatous disease.Blood 76: 602–606.

    Google Scholar 

  • Goodship J, Malcolm S, Lau YL, Pembrey ME, Levinsky RJ (1988) Use of X-chromosome inactivation analysis to establish carrier status for X-linked severe combined immunodeficiency.Lancet 1, 729–730.

    Google Scholar 

  • Goodship J, Levinsky RJ, Malcolm S (1989) Linkage of PGK1 to X-linked severe combined immunodeficiency (IMD4) allows predictive testing in families with no surviving male.Hum Genet 84: 11–14.

    Google Scholar 

  • Goodship J, Malcolm S, Levinsky RJ (1991) Evidence that X-linked severe combined immunodeficiency is not a differentiation defect of T lymphocytes.Clin Exp Immunol 83: 4–9.

    Google Scholar 

  • Goonewardena P, Sjöholm AG, Nilsson L-A, Pettersson U (1988) Linkage analysis of the properdin deficiency gene: Suggestion of a locus in the proximal part of the short arm of the X chromosome.Genomics 2: 115–118.

    Google Scholar 

  • Goundis D, Holt SM, Boyd Y, Reid KBM (1989) Localization of the properdin structural locus to Xp11.23–Xp21.1.Genomics 3: 56–60.

    Google Scholar 

  • Greer WL, Kwong PC, Peacocke M, Ip P, Rubin LA, Simonovitch KA (1989) X-Chromosome inactivation in the Wiskott-Aldrich syndrome: A marker for detection of the carrier state and identification of cell lineages expressing the gene defect.Genomics 4: 60–67.

    Google Scholar 

  • Greer WL, Somani A-K, Kwong PC, Peacocke M, Rubin LA, Simonovitch KA (1990) Linkage relationship of the Wiskott-Aldrich syndrome to 10 loci in the pericentromeric region of the human X chromosome.Genomics 6: 568–571.

    Google Scholar 

  • Guioli S, Arveiler B, Bardoni B et al (1989) Close linkage of probe p212 (DXS178) to X-linked agammaglobulinemia.Hum Genet 84: 19–21.

    Google Scholar 

  • Hendriks RW, Kraakman MEM, Craig IW, Espanol T, Schuurman RKB (1990) Evidence that in X-linked immunodeficiency with hyperimmunoglobulinemia M the intrinsic immunoglobulin heavy chain class switch mechanism is intact.Eur J Immunol 20: 2603–2608.

    Google Scholar 

  • Hendriks RW, Sandkuyl LA, Kraakman MEM, Espanol T, Schuurman RKB (1991) RFLP linkage and X chromosome inactivation analysis in X-linked immunodeficiency with hyperimmunoglobulinaemia M. In Chapel HM, Levinsky RJ, Webster ADB, eds.Progress in Immune Deficiency III, London: Royal Society of Medicine, 266–271.

    Google Scholar 

  • Kwan S-P, Terwilliger J, Parmley R et al (1990) Identification of a closely-linked DNA marker, DXS178, to further refine the X-linked agammaglobulinemia locus.Genomics 6: 238–242.

    Google Scholar 

  • Levinsky RJ, Harvey BAM, Rodeck CH, Soothill JF (1983) Phorbol-myristate acetate stimulated NBT test; a simple method suitable for antenatal diagnosis of chronic granulomatous disease of childhood.Clin Exp Immunol 54: 595–598.

    Google Scholar 

  • Malcolm S, de Saint Basile G, Arveiler B et al (1987) Close linkage of random DNA fragments from Xq21.3–22 to X-linked agammaglobulinemia (XLA).Hum Genet 77: 172–174.

    Google Scholar 

  • Mensink EJBM, Thompson A, Sandkuyl LA et al (1987) X-linked immunodeficiency with hyperimmunoglobulinemia M appears to be linked to the DXS42 restriction fragment polymorphism locus.Hum Genet 76: 96–99.

    Google Scholar 

  • Nolan KF, Schwaeble W, Kaluz S, Dierich MP, Reid KBM (1991) Molecular cloning of the cDNA coding for properdin, a positive regulator of the alternative pathway of human complement.Eur J Immunol 21: 771–776.

    Google Scholar 

  • Orkin SH (1989) Molecular genetics of chronic granulomatous disease.Annu Rev Immunol 7: 277–307.

    Google Scholar 

  • Pelham A, O'Reilly M-AJ, Malcolm S, Levinsky RJ, Kinnon C (1990) RFLP and deletion analysis for X-linked chronic granulomatous disease using the cDNA probe: Potential for improved prenatal diagnosis and carrier determination.Blood 76: 820–824.

    Google Scholar 

  • Puck JM, Nussbaum RL, Smead DL, Conley ME (1989) X-linked severe combined immunodeficiency: Localization within the region Xq13.1–q21.1 by linkage and deletion analysis.Am J Hum Genet 44: 724–730.

    Google Scholar 

  • Puck JM, Stewart CC, Conley ME, Nussbaum RL (1990) Narrowing the boundaries for X-linked severe combined immunodeficiency (SCIDX1) in Xq31.1–q21.1 by linkage and deletion analysis,Am J Hum Genet 47(3) (suppl) Abstract number (0765) 1.411.

  • Royer-Pokera B, Kunkel LM, Monaco AP et al (1986) Cloning the gene for an inherited human disorder — chronic granulomatous disease — on the basis of its chromosomal location.Nature 322: 32–38.

    Google Scholar 

  • Sanger WG, Grierson HL, Skare J et al (1990) Partial deletion in a family with the X-linked lymphoproliferative disease (XLP).Cancer Genet Cytogenet 47: 163–169.

    Google Scholar 

  • Shelley CS, Remold-O'Donnell E, Davis AE et al (1989) Molecular characterization of sialophorin (CD43), the lymphocyte surface sialoglycoprotein defective in Wiskott-Aldrich syndrome.Proc Natl Acad Sci USA 86: 2819–2823.

    Google Scholar 

  • Skare JC, Grierson HL, Sullivan JL et al (1989) Linkage analysis of seven kindreds with the X-linked lymphoproliferative syndrome (XLP) confirms that the XLP locus is near DXS42 and DXS37.Hum Genet 82: 354–358.

    Google Scholar 

  • Teahan C, Rowe P, Parker P, Totty N, Segal AW (1987) The X-linked chronic granulomatous disease gene codes for theβ-chain of cytochromeb −245.Nature 327: 720–721.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Molecular Immunology Unit, Institute of Child Health, University of London, 30 Guilford Street, WC1N 1EH, London, UK

    C. Kinnon & R. Levinsky

Authors
  1. C. Kinnon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Levinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kinnon, C., Levinsky, R. The molecular basis of X-linked immunodeficiency disease. J Inherit Metab Dis 15, 674–682 (1992). https://doi.org/10.1007/BF01799623

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01799623

Keywords

Search

Navigation