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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
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, 1986
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, 1987
Conley ME, Puck, JM: Carrier detection in typical and atypical X-linked agammaglobulinemia. J Pediat 112:688–694, 1988
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, 1989
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, 1975
Nisen PD, Waber PG: Nonrandom X chromosome DNA methylation patterns in hemophiliac females. J Clin Invest 83:1400–1403, 1989
Fasth A: Primary immunodeficiency disorders in Sweden: Cases among children, 1974–1979. J Clin Immunol 2:86–92, 1982
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, 1984
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, 1990
Therman E, Patau D: Abnormal X chromosomes in Man. Origin, behavior and effects. Hum Genet 25:1–16, 1974
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, 1989
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, 1988
Conley ME: B cells in patients with X-linked agammaglobulinemia. J Immunol 134:3070–3074, 1985
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, 1988
Conley ME, Puck JM: Definition of the gene loci in X-linked immunodeficiencies. Immunol Invest 17:425–463, 1988
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, 1987
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, 1989
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, 1989
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, 1990
WHO: Report of a WHO sponsored meeting. Primary immunodeficiency diseases. Immunodefic Rev 1:173–205, 1989
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 226–236
Lederman HM, Winkelstein JA: X-linked agammaglobulinemia: An analysis of 96 patients. Medicine 64:145–156, 1985
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, 1973
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, 1977
McKinney RE Jr, Katz SL, Wilfert CM: Chronic enteroviral meningoencephalitis in agammaglobulinemic patients. Rev Infect Dis 9:334–356, 1987
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Conley, M.E., Sweinberg, S.K. Females with a disorder phenotypically identical to X-linked agammaglobulinemia. J Clin Immunol 12, 139–143 (1992). https://doi.org/10.1007/BF00918144
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00918144