Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögren's Syndrome

Rohan Sharma, Valerie M. Harris, Joshua Cavett, Biji T. Kurien, Ke Liu, Kristi A. Koelsch, Anum Fayaaz, Kaustubh S. Chaudhari, Lida Radfar, David Lewis, Donald U. Stone, C. Erick Kaufman, Shibo Li, Barbara Segal, Daniel J. Wallace, Michael H. Weisman, Swamy Venuturupalli, Jennifer A. Kelly, Bernardo Pons-Estel, Roland JonssonXianglan Lu, Jacques Eric Gottenberg, Juan Manuel Anaya, Deborah S. Cunninghame-Graham, Andrew J.W. Huang, Michael T. Brennan, Pamela Hughes, Ilias Alevizos, Corinne Miceli-Richard, Edward C. Keystone, Vivian P. Bykerk, Gideon Hirschfield, Gunnel Nordmark, Sara Magnusson Bucher, Per Eriksson, Roald Omdal, Nelson L. Rhodus, Maureen Rischmueller, Michael Rohrer, Marie Wahren-Herlenius, Torsten Witte, Marta Alarcón-Riquelme, Xavier Mariette, Christopher J. Lessard, John B. Harley, Wan Fai Ng, Astrid Rasmussen, Kathy L. Sivils, R. Hal Scofield

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Objective: Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) are related by clinical and serologic manifestations as well as genetic risks. Both diseases are more commonly found in women than in men, at a ratio of ~10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease, suggesting a dose effect on the X chromosome. Methods: We examined cohorts of SS and SLE patients by constructing intensity plots of X chromosome single-nucleotide polymorphism alleles, along with determining the karyotype of selected patients. Results: Among ~2,500 women with SLE, we found 3 patients with a triple mosaic, consisting of 45,X/46,XX/47,XXX. Among ~2,100 women with SS, 1 patient had 45,X/46,XX/47,XXX, with a triplication of the distal p arm of the X chromosome in the 47,XXX cells. Neither the triple mosaic nor the partial triplication was found among the controls. In another SS cohort, we found a mother/daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in ~1 in 25,000–50,000 live female births, while partial triplications are even rarer. Conclusion: Very rare X chromosome abnormalities are present among patients with either SS or SLE and may inform the location of a gene(s) that mediates an X dose effect, as well as critical cell types in which such an effect is operative.

Original languageEnglish (US)
Pages (from-to)2187-2192
Number of pages6
JournalArthritis and Rheumatology
Volume69
Issue number11
DOIs
StatePublished - Nov 2017

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

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    Sharma, R., Harris, V. M., Cavett, J., Kurien, B. T., Liu, K., Koelsch, K. A., Fayaaz, A., Chaudhari, K. S., Radfar, L., Lewis, D., Stone, D. U., Kaufman, C. E., Li, S., Segal, B., Wallace, D. J., Weisman, M. H., Venuturupalli, S., Kelly, J. A., Pons-Estel, B., ... Scofield, R. H. (2017). Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögren's Syndrome. Arthritis and Rheumatology, 69(11), 2187-2192. https://doi.org/10.1002/art.40207