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; Gang Xie; Gunnel Nordmark; Sara Magnusson Bucher; Per Eriksson; Roald Omdal; Nelson L Rhodus; Maureen Rischmueller; Michael Rohrer; Marie Wahren-Herlenius; Torsten Witte; Marta Alarcon-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 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, Gang Xie, Gunnel Nordmark, Sara Magnusson Bucher, Per Eriksson, Roald Omdal, Nelson L Rhodus, Maureen Rischmueller, Michael Rohrer, Marie Wahren-Herlenius, Torsten Witte, Marta Alarcon-Riquelme, Xavier Mariette, Christopher J Lessard, John B Harley, Wan-Fai Ng, Astrid Rasmussen, Kathy L Sivils, R Hal Scofield

Immunology and Immunotherapy

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Abstract

BACKGROUND: Sjögren's syndrome and systemic lupus erythematosus (SLE) are related by clinical and serological manifestations as well as genetic risks. Both diseases are more commonly found in women compared to men at a ratio of about 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 Sjögren's syndrome or SLE patients with intensity plots of X chromosome single nucleotide polymorphism (SNP) alleles along with karyotype of selected subjects.

RESULTS: Among ∼2500 women with SLE we found three patients with a triple mosaic consisting of 45,X/46,XX/47,XXX. Among ∼2100 women with Sjögren's syndrome, one 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 were found among controls. In another Sjögren's cohort, we found a mother-daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in approximately 1 in 25,000 to 50,000 live female births, while partial triplications such are even rarer.

CONCLUSIONS: Very rare X chromosome abnormalities are present among patients with either Sjögren's or SLE, and may inform the location of a gene(s) that mediate an X dose effect as well as critical cell types in which such effect is operative. This article is protected by copyright. All rights reserved.

Original language	English
Journal	Arthritis & Rheumatology (Hoboken)
Early online date	10 Jul 2017
DOIs	https://doi.org/10.1002/art.40207
Publication status	E-pub ahead of print - 10 Jul 2017

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10.1002/art.40207Licence: None: All rights reserved

Sharma_et_al_Rare_X_chromosome_Arthritis_and_Rheumatology_2017
This is the peer reviewed version of the following article: Sharma, R., et.al, Rare X chromosome abnormalities in systemic lupus erythematosus and Sjögren's syndrome. Arthritis & Rheumatology. Accepted Author Manuscript. doi:10.1002/art.4020, which has been published in final form at 10.1002/art.4020. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Accepted author manuscript, 800 KBLicence: Other (please specify with Rights Statement)

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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 & Rheumatology (Hoboken). https://doi.org/10.1002/art.40207

@article{858411867cdb4cbba188a4a1f63a224a,

title = "Rare X chromosome abnormalities in systemic lupus erythematosus and Sj{\"o}gren's syndrome",

abstract = "BACKGROUND: Sj{\"o}gren's syndrome and systemic lupus erythematosus (SLE) are related by clinical and serological manifestations as well as genetic risks. Both diseases are more commonly found in women compared to men at a ratio of about 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 Sj{\"o}gren's syndrome or SLE patients with intensity plots of X chromosome single nucleotide polymorphism (SNP) alleles along with karyotype of selected subjects.RESULTS: Among ∼2500 women with SLE we found three patients with a triple mosaic consisting of 45,X/46,XX/47,XXX. Among ∼2100 women with Sj{\"o}gren's syndrome, one 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 were found among controls. In another Sj{\"o}gren's cohort, we found a mother-daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in approximately 1 in 25,000 to 50,000 live female births, while partial triplications such are even rarer.CONCLUSIONS: Very rare X chromosome abnormalities are present among patients with either Sj{\"o}gren's or SLE, and may inform the location of a gene(s) that mediate an X dose effect as well as critical cell types in which such effect is operative. This article is protected by copyright. All rights reserved.",

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 Jacques-Eric Gottenberg and Juan-Manuel Anaya 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 Gang Xie 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 Alarcon-Riquelme and Xavier Mariette and Lessard, {Christopher J} and Harley, {John B} and Wan-Fai Ng and Astrid Rasmussen and Sivils, {Kathy L} and Scofield, {R Hal}",

note = "{\textcopyright} 2017, American College of Rheumatology.",

year = "2017",

month = jul,

day = "10",

doi = "10.1002/art.40207",

language = "English",

journal = "Arthritis & Rheumatology (Hoboken)",

issn = "2326-5191",

publisher = "Wiley",

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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, J-E, Anaya, J-M, Cunninghame-Graham, DS, Huang, AJW, Brennan, MT, Hughes, P, Alevizos, I, Miceli-Richard, C, Keystone, EC, Bykerk, VP, Hirschfield, G, Xie, G, Nordmark, G, Bucher, SM, Eriksson, P, Omdal, R, Rhodus, NL, Rischmueller, M, Rohrer, M, Wahren-Herlenius, M, Witte, T, Alarcon-Riquelme, M, Mariette, X, Lessard, CJ, Harley, JB, Ng, W-F, Rasmussen, A, Sivils, KL & Scofield, RH 2017, 'Rare X chromosome abnormalities in systemic lupus erythematosus and Sjögren's syndrome', Arthritis & Rheumatology (Hoboken). 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 - Xie, Gang

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 - Alarcon-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 - 2017/7/10

Y1 - 2017/7/10

N2 - BACKGROUND: Sjögren's syndrome and systemic lupus erythematosus (SLE) are related by clinical and serological manifestations as well as genetic risks. Both diseases are more commonly found in women compared to men at a ratio of about 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 Sjögren's syndrome or SLE patients with intensity plots of X chromosome single nucleotide polymorphism (SNP) alleles along with karyotype of selected subjects.RESULTS: Among ∼2500 women with SLE we found three patients with a triple mosaic consisting of 45,X/46,XX/47,XXX. Among ∼2100 women with Sjögren's syndrome, one 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 were found among controls. In another Sjögren's cohort, we found a mother-daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in approximately 1 in 25,000 to 50,000 live female births, while partial triplications such are even rarer.CONCLUSIONS: Very rare X chromosome abnormalities are present among patients with either Sjögren's or SLE, and may inform the location of a gene(s) that mediate an X dose effect as well as critical cell types in which such effect is operative. This article is protected by copyright. All rights reserved.

AB - BACKGROUND: Sjögren's syndrome and systemic lupus erythematosus (SLE) are related by clinical and serological manifestations as well as genetic risks. Both diseases are more commonly found in women compared to men at a ratio of about 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 Sjögren's syndrome or SLE patients with intensity plots of X chromosome single nucleotide polymorphism (SNP) alleles along with karyotype of selected subjects.RESULTS: Among ∼2500 women with SLE we found three patients with a triple mosaic consisting of 45,X/46,XX/47,XXX. Among ∼2100 women with Sjögren's syndrome, one 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 were found among controls. In another Sjögren's cohort, we found a mother-daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in approximately 1 in 25,000 to 50,000 live female births, while partial triplications such are even rarer.CONCLUSIONS: Very rare X chromosome abnormalities are present among patients with either Sjögren's or SLE, and may inform the location of a gene(s) that mediate an X dose effect as well as critical cell types in which such effect is operative. This article is protected by copyright. All rights reserved.

U2 - 10.1002/art.40207

DO - 10.1002/art.40207

M3 - Article

C2 - 28692793

SN - 2326-5191

JO - Arthritis & Rheumatology (Hoboken)

JF - Arthritis & Rheumatology (Hoboken)

ER -

Rare X chromosome abnormalities in systemic lupus erythematosus and Sjögren's syndrome

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