Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Sjögren’s syndrome and systemic lupus erythematosus (SLE) are chronic, autoimmune diseases that are related by clinical and serological manifestations as well as genetic risks. Both diseases are much more commonly found in women compared to men at a ratio of about 10 to 1. We have previously shown that relatively common X chromosome aneuploidies, 47XXY (Klinefelter’s syndrome, 1 in 500 live male births) and 47XXX (1 in 1000 live female births), are enriched among men and women, respectively, with Sjögren’s or SLE. We undertook this study to describe rare X chromosome aneuploidies among large cohorts of patients with these diseases.
Methods: We examined large cohorts of Sjögren’s syndrome or SLE patients with intensity plots of X chromosome single nucleotide polymorphism (SNP) alleles. In addition, we also carried out karyotype of peripheral blood mononuclear cells from Sjögren’s syndrome and SLE subjects.
Results: Among 2,426 women with SLE we found three patients with a triple mosaic consisting of 45X/46XX/47XXX, a statistically significant increase compared to controls and the known birth rate by binomial confidence intervals. Among 2138 women with Sjögren’s syndrome, one patient had 45X/46XX/47XXX with a triplication of the distal p arm of the X chromosome in the 47XXX cells. Neither the triple mosaic nor a partial triplication were found among controls. In fact, the triple mosaic occurs in approximately 1 in 25,000 to 50,000 live female births, while a partial triplication such as the one found is even rarer. In another cohort of Sjögren’s patients, we found a mother-daughter pair in which the mother had an inversion of the proximal region of Xq and the daughter had a Xp isochrome with partial triplication of distal Xp.
Conclusion: Very rare X chromosome abnormalities are present among patients with either Sjögren’s or SLE. These rare variants may be informative as to location of a gene or genes on the X chromosome that mediate a gene dose effect as well as critical cell types in which a gene dose effect is operative.
To cite this abstract in AMA style:Sharma R, Harris VM, Cavett J, Kurien BT, Liu K, Koelsch KA, Radfar L, Lewis DM, Stone DU, Kaufman CE, Li S, Segal BM, Wallace DJ, Weisman M, Kelly JA, Pons-Estel B, Jonsson R, Gottenberg JE, Anaya JM, Cunninghame-Graham DS, Bykerk VP, Hirschfield G, Xie G, Ng WF, Nordmark G, Eriksson P, Omdal R, Rhodus NL, Rischmueller M, Rohrer MD, Wahren-Herlenius M, Witte T, Mariette X, Lessard CJ, Harley JB, Sivils KL, Rasmussen A, Scofield RH, Venturopalli S, Lu X, Hughes P, Huang AJW, Miceli-Richard C. Very Rare X Chromosome Abnormalities in SLE and SjöGren’s May Localize X Gene Dose Effect [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/very-rare-x-chromosome-abnormalities-in-sle-and-sjogrens-may-localize-x-gene-dose-effect/. Accessed February 29, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/very-rare-x-chromosome-abnormalities-in-sle-and-sjogrens-may-localize-x-gene-dose-effect/