Rohan Sharma1, Valerie M Harris2, Joshua Cavett2, Biji T Kurien1, Ke Liu3, Kristi A Koelsch1, Anum Fayaaz4, Kaustubh S Chaudhari4, Lida Radfar5, David Lewis5, Donald U Stone6, C Erick Kaufman5, Shibo Li5, Barbara Segal7, Daniel J Wallace8, Michael H Weisman8, Swamy Venuturupalli8, Jennifer A Kelly9, Bernardo Pons-Estel10, Roland Jonsson11, Xianglan Lu5, Jacques-Eric Gottenberg12, Juan-Manuel Anaya13, Deborah S Cunninghame-Graham14, Andrew J W Huang15, Michael T Brennan16, Pamela Hughes15, Ilias Alevizos17, Corinne Miceli-Richard18, Edward C Keystone19, Vivian P Bykerk20, Gideon Hirschfield21, Gunnel Nordmark22, Sara Magnusson Bucher23, Per Eriksson24, Roald Omdal25, Nelson L Rhodus15, Maureen Rischmueller26, Michael Rohrer15, Marie Wahren-Herlenius27, Torsten Witte28, Marta Alarcón-Riquelme29, Xavier Mariette18, Christopher J Lessard9, John B Harley30, Wan-Fai Ng31, Astrid Rasmussen9, Kathy L Sivils2, R Hal Scofield1. 1. Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, and Department of Veterans Affairs Medical Center, Oklahoma City. 2. Oklahoma Medical Research Foundation and University of Oklahoma Health Sciences Center, Oklahoma City. 3. Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio. 4. Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma. 5. University of Oklahoma Health Sciences Center, Oklahoma City. 6. Johns Hopkins University, Baltimore, Maryland, and King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. 7. University of Minnesota Medical School, Minneapolis. 8. Cedars-Sinai Medical Center, Los Angeles, California. 9. Oklahoma Medical Research Foundation, Oklahoma City. 10. Sanatorio Parque, Rosario, Argentina. 11. University of Bergen and Haukeland University Hospital, Bergen, Norway. 12. Strasbourg University, Strasbourg, France. 13. Universidad del Rosario, Bogota, Colombia. 14. King's College London, London, UK. 15. University of Minnesota, Minneapolis. 16. Carolinas Medical Center, Charlotte, North Carolina. 17. National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD. 18. Department of Rheumatology, Université Paris-Sud, AP-HP, INSERM U1012, Le Kremlin-Bicêtre, France. 19. Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada. 20. Hospital for Special Surgery, New York, New York. 21. University of Birmingham, Birmingham, UK. 22. Uppsala University, Uppsala, Sweden. 23. Örebro University Hospital, Örebro, Sweden. 24. Linköping University, Linköping, Sweden. 25. Stavanger University Hospital, Stavanger, Norway. 26. The Queen Elizabeth Hospital, Woodville South, and University of Adelaide, Adelaide, South Australia, Australia. 27. Karolinska Institutet, Stockholm, Sweden. 28. Hannover Medical School, Hannover, Germany. 29. Pfizer-University of Granada-Andalusian Regional Government, Granada, Spain, and Karolinska Institutet, Stockholm, Sweden. 30. Cincinnati Children's Hospital Medical Center, University of Cincinnati, and Ohio Department of Veterans Affairs Medical Center, Cincinnati. 31. Newcastle University, Newcastle upon Tyne, UK.
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.
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 SLEpatients 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.
Authors: Amr H Sawalha; Lu Wang; Ajay Nadig; Emily C Somers; W Joseph McCune; Travis Hughes; Joan T Merrill; R Hal Scofield; Faith M Strickland; Bruce Richardson Journal: J Autoimmun Date: 2012-02-03 Impact factor: 7.094
Authors: Ming Zhao; Siyang Liu; Shuangyan Luo; Honglong Wu; Meini Tang; Wenjing Cheng; Qing Zhang; Peng Zhang; Xinhai Yu; Yudong Xia; Na Yi; Fei Gao; Li Wang; Susan Yung; Tak Mao Chan; Amr H Sawalha; Bruce Richardson; M Eric Gershwin; Ning Li; Qianjin Lu Journal: J Autoimmun Date: 2014-08-03 Impact factor: 7.094
Authors: Valerie M Harris; Rohan Sharma; Joshua Cavett; Biji T Kurien; Ke Liu; Kristi A Koelsch; Astrid Rasmussen; 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; Marta E Alarcon-Riquelme; 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; Katherine A Siminovitch; Wan-Fai Ng; Gunnel Nordmark; Sara Magnusson Bucher; Per Eriksson; Roald Omdal; Nelson L Rhodus; Maureen Rischmueller; Michael Rohrer; Marie Wahren-Herlenius; Torsten Witte; Xavier Mariette; Christopher J Lessard; John B Harley; Kathy L Sivils; R Hal Scofield Journal: Clin Immunol Date: 2016-04-22 Impact factor: 3.969
Authors: F J Jiménez-Balderas; R Tápia-Serrano; M E Fonseca; J Arellano; A Beltrán; P Yáñez; A Camargo-Coronel; A Fraga Journal: Arthritis Res Date: 2001-09-12
Authors: C M Cooney; G R Bruner; T Aberle; B Namjou-Khales; L K Myers; L Feo; S Li; A D'Souza; A Ramirez; J B Harley; R H Scofield Journal: Genes Immun Date: 2009-05-21 Impact factor: 2.676
Authors: Rohan Sharma; Kaustubh S Chaudhari; Biji T Kurien; Kiely Grundahl; Lida Radfar; David M Lewis; Christopher J Lessard; He Li; Astrid Rasmussen; Kathy L Sivils; R Hal Scofield Journal: J Rheumatol Date: 2019-05-15 Impact factor: 4.666