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 Jonsson; Xianglan 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

doi:10.1002/art.40207

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 Jonsson

Xianglan 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

University of Oklahoma
Cincinnati Children's Hospital Medical Center
Department of Veterans Affairs
Johns Hopkins University
King Khaled Eye Specialist Hospital
University of Minnesota Twin Cities
Cedars-Sinai Medical Center
Oklahoma Medical Research Foundation
Sanatorio Parque
University of Bergen
Université de Strasbourg
Universidad del Rosario
King's College London
Carolinas Medical Center
National Institutes of Health
Université Paris-Saclay
University of Toronto
Hospital for Special Surgery - New York
University of Birmingham
Uppsala University
Örebro University
Linköping University
Stavanger University Hospital
University of Adelaide
Karolinska Institutet
Hannover Medical School
Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO)
VA Medical Center
Newcastle University

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	2187-2192
Number of pages	6
Journal	Arthritis and Rheumatology
Volume	69
Issue number	11
DOIs	https://doi.org/10.1002/art.40207
Publication status	Published - Nov 2017
Externally published	Yes

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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

@article{b792edf6b35247bc8ac19b0797a5c2ac,

title = "Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sj{\"o}gren's Syndrome",

abstract = "Objective: Sj{\"o}gren'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 \textasciitilde{}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 \textasciitilde{}2,500 women with SLE, we found 3 patients with a triple mosaic, consisting of 45,X/46,XX/47,XXX. Among \textasciitilde{}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 \textasciitilde{}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.",

author = "Rohan Sharma and Harris, \{Valerie M.\} and Joshua Cavett and Kurien, \{Biji T.\} and Ke Liu and Koelsch, \{Kristi A.\} and Anum Fayaaz and Chaudhari, \{Kaustubh S.\} and Lida Radfar and David Lewis and Stone, \{Donald U.\} and Kaufman, \{C. Erick\} and Shibo Li and Barbara Segal and Wallace, \{Daniel J.\} and Weisman, \{Michael H.\} and Swamy Venuturupalli and Kelly, \{Jennifer A.\} and Bernardo Pons-Estel and Roland Jonsson and Xianglan Lu and Gottenberg, \{Jacques Eric\} and Anaya, \{Juan Manuel\} and Cunninghame-Graham, \{Deborah S.\} and Huang, \{Andrew J.W.\} and Brennan, \{Michael T.\} and Pamela Hughes and Ilias Alevizos and Corinne Miceli-Richard and Keystone, \{Edward C.\} and Bykerk, \{Vivian P.\} and Gideon Hirschfield and Gunnel Nordmark and Bucher, \{Sara Magnusson\} and Per Eriksson and Roald Omdal and Rhodus, \{Nelson L.\} and Maureen Rischmueller and Michael Rohrer and Marie Wahren-Herlenius and Torsten Witte and Marta Alarc{\'o}n-Riquelme and Xavier Mariette and Lessard, \{Christopher J.\} and Harley, \{John B.\} and Ng, \{Wan Fai\} and Astrid Rasmussen and Sivils, \{Kathy L.\} and Scofield, \{R. Hal\}",

note = "Publisher Copyright: {\textcopyright} 2017, American College of Rheumatology",

year = "2017",

month = nov,

doi = "10.1002/art.40207",

language = "English",

volume = "69",

pages = "2187--2192",

journal = "Arthritis and Rheumatology",

issn = "2326-5191",

publisher = "John Wiley and Sons Ltd",

number = "11",

}

Sharma, R, Harris, VM, Cavett, J, Kurien, BT, Liu, K, Koelsch, KA, Fayaaz, A, Chaudhari, KS, Radfar, L, Lewis, D, Stone, DU, Kaufman, CE, Li, S, Segal, B, Wallace, DJ, Weisman, MH, Venuturupalli, S, Kelly, JA, Pons-Estel, B, Jonsson, R, Lu, X, Gottenberg, JE, Anaya, JM, Cunninghame-Graham, DS, Huang, AJW, Brennan, MT, Hughes, P, Alevizos, I, Miceli-Richard, C, Keystone, EC, Bykerk, VP, Hirschfield, G, Nordmark, G, Bucher, SM, Eriksson, P, Omdal, R, Rhodus, NL, Rischmueller, M, Rohrer, M, Wahren-Herlenius, M, Witte, T, Alarcón-Riquelme, M, Mariette, X, Lessard, CJ, Harley, JB, Ng, WF, Rasmussen, A, Sivils, KL & Scofield, RH 2017, 'Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögren's Syndrome', Arthritis and Rheumatology, vol. 69, no. 11, pp. 2187-2192. https://doi.org/10.1002/art.40207

TY - JOUR

T1 - Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögren's Syndrome

AU - Sharma, Rohan

AU - Harris, Valerie M.

AU - Cavett, Joshua

AU - Kurien, Biji T.

AU - Liu, Ke

AU - Koelsch, Kristi A.

AU - Fayaaz, Anum

AU - Chaudhari, Kaustubh S.

AU - Radfar, Lida

AU - Lewis, David

AU - Stone, Donald U.

AU - Kaufman, C. Erick

AU - Li, Shibo

AU - Segal, Barbara

AU - Wallace, Daniel J.

AU - Weisman, Michael H.

AU - Venuturupalli, Swamy

AU - Kelly, Jennifer A.

AU - Pons-Estel, Bernardo

AU - Jonsson, Roland

AU - Lu, Xianglan

AU - Gottenberg, Jacques Eric

AU - Anaya, Juan Manuel

AU - Cunninghame-Graham, Deborah S.

AU - Huang, Andrew J.W.

AU - Brennan, Michael T.

AU - Hughes, Pamela

AU - Alevizos, Ilias

AU - Miceli-Richard, Corinne

AU - Keystone, Edward C.

AU - Bykerk, Vivian P.

AU - Hirschfield, Gideon

AU - Nordmark, Gunnel

AU - Bucher, Sara Magnusson

AU - Eriksson, Per

AU - Omdal, Roald

AU - Rhodus, Nelson L.

AU - Rischmueller, Maureen

AU - Rohrer, Michael

AU - Wahren-Herlenius, Marie

AU - Witte, Torsten

AU - Alarcón-Riquelme, Marta

AU - Mariette, Xavier

AU - Lessard, Christopher J.

AU - Harley, John B.

AU - Ng, Wan Fai

AU - Rasmussen, Astrid

AU - Sivils, Kathy L.

AU - Scofield, R. Hal

PY - 2017/11

Y1 - 2017/11

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85031328096

U2 - 10.1002/art.40207

DO - 10.1002/art.40207

M3 - Article

C2 - 28692793

AN - SCOPUS:85031328096

SN - 2326-5191

VL - 69

SP - 2187

EP - 2192

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

IS - 11

ER -

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

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