Abstract
Systemic lupus erythematosus (SLE) disproportionately affects women. Recent work demonstrates that men with Klinefelter's syndrome (47,XXY men) have a similar risk of developing SLE as do women. We present an unusual African-American family with two SLE-affected individuals in which one of the patients with SLE also has Turner's syndrome (46,X,del(X)(q13)). Although not definitive, this family raises interesting questions regarding the function of genes located on the X chromosome in the development of SLE. The paucity of case reports documenting the overlap of SLE with Turner's syndrome while there is an association of male SLE with Klinefelter's syndrome suggests a lower risk of SLE in women with Turner's syndrome. These observations are consistent with a gene dose effect at X with two X chromosomes (46,XX or 47,XXY) conferring higher risk and one X chromosome (46,XY or 45,XO) conferring lower risk of SLE.
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References
Wallace DJ, Hahn BH . Dubois’ Lupus Erythematosus, 7th edn, Lippincott Williams & Wilkins: Philadelphia, 2007.
Fessel WJ . Systemic lupus erythematosus in the community. Incidence, prevalence, outcome, and first symptoms; the high prevalence in black women. Arch Intern Med 1974; 134: 1027–1035.
McCarty DJ, Manzi S, Medsger Jr TA, Ramsey-Goldman R, LaPorte RE, Kwoh CK . Incidence of systemic lupus erythematosus. Race and gender differences. Arthritis Rheum 1995; 38: 1260–1270.
Scofield RH, Bruner GR, Namjou B, Kimberly RP, Ramsey-Goldman R, Petri M et al. Klinefelter's syndrome, 47,XXY, in male systemic lupus erythematosus supports a gene dose effect from the X chromosome. Arthritis Rheum 2008; 58: 2511–2517.
Turner HH . A syndrome of infantilism, congenital webbed neck, and cubitus valgus. Endocrinology 1938; 23: 566.
Ford CE, Jones KW, Polani PE, De Almeida JC, Briggs JH . A sex-chromosome anomaly in a case of gonadal dysgenesis (Turner's syndrome). Lancet 1959; 1: 711–713.
Takegami T, Nakao K, Nagayama Y, Fujita T, Hoshino T, Tsunematsu T et al. [A case of SLE associated with Turner's syndrome of 45, XO/46, XXq+ mosaicism (author's transl)]. Nippon Naika Gakkai Zasshi 1980; 69: 861–866.
Rakfal SM, Deutsch M . Radiotherapy for malignancies associated with lupus: case reports of acute and late reactions. Am J Clin Oncol 1998; 21: 54–57.
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.
Hochberg MC . Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725.
Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW . Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. Am J Hum Genet 1992; 51: 1229–1239.
MacLaughlin DT, Donahoe PK . Sex determination and differentiation. N Engl J Med 2004; 350: 367–378.
Invernizzi P, Miozzo M, Oertelt-Prigione S, Meroni PL, Persani L, Selmi C et al. X monosomy in female systemic lupus erythematosus. Ann NY Acad Sci 2007; 1110: 84–91.
Invernizzi P, Pasini S, Selmi C, Miozzo M, Podda M . Skewing of X chromosome inactivation in autoimmunity. Autoimmunity 2008; 41: 272–277.
Chitnis S, Monteiro J, Glass D, Apatoff B, Salmon J, Concannon P et al. The role of X-chromosome inactivation in female predisposition to autoimmunity. Arthritis Res 2000; 2: 399–406.
Selmi C, Invernizzi P, Gershwin ME . The X chromosome and systemic sclerosis. Curr Op Rheumatol 2006; 18: 601–605.
Huang Q, Parfitt A, Grennan DM, Manolios N . X-chromosome inactivation in monozygotic twins with systemic lupus erythematosus. Autoimmunity 1997; 26: 85–93.
Hayward PA, Satsangi J, Jewell DP . Inflammatory bowel disease and the X chromosome. QJM 1996; 89: 713–718.
Elsheikh M, Wass JA, Conway GS . Autoimmune thyroid syndrome in women with Turner's syndrome—the association with karyotype. Clin Endocrinol 2001; 55: 223–226.
Bonamico M, Bottaro G, Pasquino AM, Caruso-Nicoletti M, Mariani P, Gemme G et al. Celiac disease and Turner syndrome. J Pediatr Gastroenterol Nutrit 1998; 26: 496–499.
Bettendorf M, Doerr HG, Hauffa BP, Lindberg A, Mehls O, Partsch CJ et al. Prevalence of autoantibodies associated with thyroid and celiac disease in Ullrich-Turner syndrome in relation to adult height after growth hormone treatment. J Pediatr Endocrinol 2006; 19: 149–154.
Rovensky J . Rheumatic diseases and Klinefelter's syndrome. Autoimmun Rev 2006; 6: 33–36.
Sidhu SK, Minks J, Chang SC, Cotton AM, Brown CJ . X chromosome inactivation: heterogeneity of heterochromatin. Biochem Cell Biol 2008; 86: 370–379.
Lu Q, Wu A, Tesmer L, Ray D, Yousif N, Richardson B . Demethylation of CD40LG on the inactive X in T cells from women with lupus. J Immunol 2007; 179: 6352–6358.
Jacob CO, Reiff A, Armstrong DL, Myones BL, Silverman E, Klein-Gitelman M et al. Identification of novel susceptibility genes in childhood-onset systemic lupus erythematosus using a uniquely designed candidate gene pathway platform. Arthritis Rheum 2007; 56: 4164–4173.
Sawalha AH, Webb R, Han S, Kelly JA, Kaufman KM, Kimberly RP et al. Common variants within MECP2 confer risk of systemic lupus erythematosus. PLoS One 2008; 3: e1727.
Acknowledgements
We especially thank the Lupus Family Registry and Repository staff for their hard work and data collection, and all our referring physicians whose lupus patient referrals make this work possible. Ms Ramirez was an OMRF Fleming Scholar while portions of this work were carried out. This study was funded by the following NIH grants: AR62277, AR053734, AI24717 and AR42460.
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Cooney, C., Bruner, G., Aberle, T. et al. 46,X,del(X)(q13) Turner's syndrome women with systemic lupus erythematosus in a pedigree multiplex for SLE. Genes Immun 10, 478–481 (2009). https://doi.org/10.1038/gene.2009.37
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DOI: https://doi.org/10.1038/gene.2009.37
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