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Brief Report: Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögren's Syndrome
Author(s) -
Sharma Rohan,
Harris Valerie M.,
Cavett Joshua,
Kurien Biji T.,
Liu Ke,
Koelsch Kristi A.,
Fayaaz Anum,
Chaudhari Kaustubh S.,
Radfar Lida,
Lewis David,
Stone Donald U.,
Kaufman C. Erick,
Li Shibo,
Segal Barbara,
Wallace Daniel J.,
Weisman Michael H.,
Venuturupalli Swamy,
Kelly Jennifer A.,
PonsEstel Bernardo,
Jonsson Roland,
Lu Xianglan,
Gottenberg JacquesEric,
Anaya JuanManuel,
CunninghameGraham Deborah S.,
Huang Andrew J. W.,
Brennan Michael T.,
Hughes Pamela,
Alevizos Ilias,
MiceliRichard Corinne,
Keystone Edward C.,
Bykerk Vivian P.,
Hirschfield Gideon,
Nordmark Gunnel,
Bucher Sara Magnusson,
Eriksson Per,
Omdal Roald,
Rhodus Nelson L.,
Rischmueller Maureen,
Rohrer Michael,
WahrenHerlenius Marie,
Witte Torsten,
AlarcónRiquelme Marta,
Mariette Xavier,
Lessard Christopher J.,
Harley John B.,
Ng WanFai,
Rasmussen Astrid,
Sivils Kathy L.,
Scofield R. Hal
Publication year - 2017
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40207
Subject(s) - chromosome , karyotype , x chromosome , medicine , cohort , genetics , immunology , gastroenterology , biology , gene
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.