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Logo of jcinvestThe Journal of Clinical Investigation
J Clin Invest. 1987 May; 79(5): 1395–1400.
PMCID: PMC424401

Carrier detection in X-linked severe combined immunodeficiency based on patterns of X chromosome inactivation.


The X-linked form of severe combined immunodeficiency (XSCID) is underdiagnosed because no methods have been available for detecting carriers. Although boys with XSCID are deficient in T cells, female carriers are immunologically normal. Carriers' normal immune function would be expected if all their T cells were derived from precursors whose X chromosome bearing the XSCID mutation was inactivated early in embryogenesis. Using somatic cell hybridization to separate the active and inactive X chromosomes and restriction fragment length polymorphisms to distinguish them, we have determined the lymphocyte X inactivation pattern in XSCID carriers and their female relatives. In the T cells of three carriers, the X chromosome bearing the XSCID mutation was consistently inactive. Nonrandom X inactivation was also found in the T cells of one at-risk female, while two others had normal, random X inactivation. This method constitutes a generally applicable carrier test for XSCID.

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Selected References

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  • Gelfand EW, Dosch HM. Diagnosis and classification of severe combined immunodeficiency disease. Birth Defects Orig Artic Ser. 1983;19(3):65–72. [PubMed]
  • Buckley RH, Schiff SE, Sampson HA, Schiff RI, Markert ML, Knutsen AP, Hershfield MS, Huang AT, Mickey GH, Ward FE. Development of immunity in human severe primary T cell deficiency following haploidentical bone marrow stem cell transplantation. J Immunol. 1986 Apr 1;136(7):2398–2407. [PubMed]
  • Hirschhorn R. Genetic deficiencies of adenosine deaminase and purine nucleoside phosphorylase: overview, genetic heterogeneity and therapy. Birth Defects Orig Artic Ser. 1983;19(3):73–81. [PubMed]
  • Botstein D, White RL, Skolnick M, Davis RW. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet. 1980 May;32(3):314–331. [PubMed]
  • Fireman P, Johnson HA, Gitlin D. Presence of plasma cells and gamma-1-M-globulin synthesis in a patient with thymic alymphoplasia. Pediatrics. 1966 Mar;37(3):485–492. [PubMed]
  • Conley ME, Nowell PC, Henle G, Douglas SD. XX T cells and XY B cells in two patients with severe combined immune deficiency. Clin Immunol Immunopathol. 1984 Apr;31(1):87–95. [PubMed]
  • Conley ME, Bartelt MS. In vitro regulation of IgA subclass synthesis. II. The source of IgA2 plasma cells. J Immunol. 1984 Nov;133(5):2312–2316. [PubMed]
  • Trinchieri G, Perussia B. Human natural killer cells: biologic and pathologic aspects. Lab Invest. 1984 May;50(5):489–513. [PubMed]
  • 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. 1986 Aug 28;315(9):564–567. [PubMed]
  • Wilson JM, Baugher BW, Mattes PM, Daddona PE, Kelley WN. Human hypoxanthine-guanine phosphoribosyltransferase. Demonstration of structural variants in lymphoblastoid cells derived from patients with a deficiency of the enzyme. J Clin Invest. 1982 Mar;69(3):706–715. [PMC free article] [PubMed]
  • Nussbaum RL, Airhart SD, Ledbetter DH. Expression of the fragile (X) chromosome in an interspecific somatic cell hybrid. Hum Genet. 1983;64(2):148–150. [PubMed]
  • Fuscoe JC, Fenwick RG, Jr, Ledbetter DH, Caskey CT. Deletion and amplification of the HGPRT locus in Chinese hamster cells. Mol Cell Biol. 1983 Jun;3(6):1086–1096. [PMC free article] [PubMed]
  • Nussbaum RL, Crowder WE, Nyhan WL, Caskey CT. A three-allele restriction-fragment-length polymorphism at the hypoxanthine phosphoribosyltransferase locus in man. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4035–4039. [PubMed]
  • Aldridge J, Kunkel L, Bruns G, Tantravahi U, Lalande M, Brewster T, Moreau E, Wilson M, Bromley W, Roderick T, et al. A strategy to reveal high-frequency RFLPs along the human X chromosome. Am J Hum Genet. 1984 May;36(3):546–564. [PubMed]
  • Reed KC, Mann DA. Rapid transfer of DNA from agarose gels to nylon membranes. Nucleic Acids Res. 1985 Oct 25;13(20):7207–7221. [PMC free article] [PubMed]
  • Boggs BA, Nussbaum RL. Two anonymous X-specific human sequences detecting restriction fragment length polymorphisms in region Xq26----qter. Somat Cell Mol Genet. 1984 Nov;10(6):607–613. [PubMed]
  • Winship PR, Anson DS, Rizza CR, Brownlee GG. Carrier detection in haemophilia B using two further intragenic restriction fragment length polymorphisms. Nucleic Acids Res. 1984 Dec 11;12(23):8861–8872. [PMC free article] [PubMed]
  • MORTON NE. Sequential tests for the detection of linkage. Am J Hum Genet. 1955 Sep;7(3):277–318. [PubMed]
  • Goodfellow PN, Davies KE, Ropers HH. Report of the Committee on the Genetic Constitution of the X and Y Chromosomes. Cytogenet Cell Genet. 1985;40(1-4):296–352. [PubMed]
  • Nyhan WL, Bakay B, Connor JD, Marks JF, Keele DK. Hemizygous expression of glucose-6-phosphate dehydrogenase in erythrocytes of heterozygotes for the Lesch-Nyhan syndrome. Proc Natl Acad Sci U S A. 1970 Jan;65(1):214–218. [PubMed]
  • Migeon BR, Moser HW, Moser AB, Axelman J, Sillence D, Norum RA. Adrenoleukodystrophy: evidence for X linkage, inactivation, and selection favoring the mutant allele in heterozygous cells. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5066–5070. [PubMed]
  • Wieacker P, Zimmer J, Ropers HH. X inactivation patterns in two syndromes with probable X-linked dominant, male lethal inheritance. Clin Genet. 1985 Sep;28(3):238–242. [PubMed]
  • Nahm MH, Paslay JW, Davie JM. Unbalanced X chromosome mosaicism in B cells of mice with X-linked immunodeficiency. J Exp Med. 1983 Sep 1;158(3):920–931. [PMC free article] [PubMed]
  • Gealy WJ, Dwyer JM, Harley JB. Allelic exclusion of glucose-6-phosphate dehydrogenase in platelets and T lymphocytes from a Wiskott-Aldrich syndrome carrier. Lancet. 1980 Jan 12;1(8159):63–65. [PubMed]
  • Prchal JT, Carroll AJ, Prchal JF, Crist WM, Skalka HW, Gealy WJ, Harley J, Malluh A. Wiskott-Aldrich syndrome: cellular impairments and their implication for carrier detection. Blood. 1980 Dec;56(6):1048–1054. [PubMed]

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