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

12 Citations (Scopus)

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 1 2017

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X Chromosome
Chromosome Aberrations
Systemic Lupus Erythematosus
Live Birth
Aneuploidy
Nuclear Family
Karyotype
Single Nucleotide Polymorphism
Alleles
Mothers
Genes

Cite this

Sharma, R., Harris, V. M., Cavett, J., Kurien, B. T., Liu, K., Koelsch, K. A., ... 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

Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögren's Syndrome. / 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.; Pons-Estel, Bernardo; Jonsson, Roland; Lu, Xianglan; Gottenberg, Jacques Eric; Anaya, Juan Manuel; Cunninghame-Graham, Deborah S.; Huang, Andrew J.W.; Brennan, Michael T.; Hughes, Pamela; Alevizos, Ilias; Miceli-Richard, 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; Wahren-Herlenius, Marie; Witte, Torsten; Alarcón-Riquelme, Marta; Mariette, Xavier; Lessard, Christopher J.; Harley, John B.; Ng, Wan Fai; Rasmussen, Astrid; Sivils, Kathy L.; Scofield, R. Hal.

In: Arthritis and Rheumatology, Vol. 69, No. 11, 01.11.2017, p. 2187-2192.

Research output: Contribution to journalArticle

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
Sharma R, Harris VM, Cavett J, Kurien BT, Liu K, Koelsch KA et al. Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögren's Syndrome. Arthritis and Rheumatology. 2017 Nov 1;69(11):2187-2192. https://doi.org/10.1002/art.40207
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. ; Pons-Estel, Bernardo ; Jonsson, Roland ; Lu, Xianglan ; Gottenberg, Jacques Eric ; Anaya, Juan Manuel ; Cunninghame-Graham, Deborah S. ; Huang, Andrew J.W. ; Brennan, Michael T. ; Hughes, Pamela ; Alevizos, Ilias ; Miceli-Richard, 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 ; Wahren-Herlenius, Marie ; Witte, Torsten ; Alarcón-Riquelme, Marta ; Mariette, Xavier ; Lessard, Christopher J. ; Harley, John B. ; Ng, Wan Fai ; Rasmussen, Astrid ; Sivils, Kathy L. ; Scofield, R. Hal. / Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögren's Syndrome. In: Arthritis and Rheumatology. 2017 ; Vol. 69, No. 11. pp. 2187-2192.
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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 ~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.",
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}",
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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 - 2017/11/1

Y1 - 2017/11/1

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.

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