PMID- 18668569 OWN - NLM STAT- MEDLINE DCOM- 20080918 LR - 20220408 IS - 0004-3591 (Print) IS - 1529-0131 (Electronic) IS - 0004-3591 (Linking) VI - 58 IP - 8 DP - 2008 Aug TI - Klinefelter's syndrome (47,XXY) in male systemic lupus erythematosus patients: support for the notion of a gene-dose effect from the X chromosome. PG - 2511-7 LID - 10.1002/art.23701 [doi] AB - OBJECTIVE: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that predominantly affects women. Despite isolated reports of patients with coexisting Klinefelter's syndrome (47,XXY) and SLE, no association of Klinefelter's syndrome with SLE or any other autoimmune disease has been established. The present study was undertaken to investigate the prevalence of Klinefelter's syndrome in a large population of patients with SLE. METHODS: Sex chromosome genotyping was performed in 981 SLE patients, of whom 213 were men. A first group of 844 SLE patients from 378 multiplex families and a second group of 137 men with nonfamilial SLE were evaluated. In selected cases, chromosomes were enumerated by fluorescence in situ hybridization (FISH) and karyotyping in transformed B cell lines. RESULTS: Of 213 men with SLE, 5 had Klinefelter's syndrome (1 in 43). Four of them were heterozygous at X markers, and Klinefelter's syndrome was confirmed by FISH and karyotyping in the fifth. An overall rate of 47,XXY of 235 per 10,000 male SLE patients was found (95% confidence interval 77-539), a dramatic increase over the known prevalence of Klinefelter's syndrome in an unselected population (17 per 10,000 live male births). Asking men with SLE about fertility was highly sensitive (100%) for Klinefelter's syndrome. All 768 women with SLE were heterozygous at X. CONCLUSION: The frequency of Klinefelter's syndrome (47,XXY), often subclinical, is increased in men with SLE by approximately 14-fold compared with its prevalence in men without SLE. Diagnostic vigilance for 47,XXY in male patients with SLE is warranted. These data are the first to show an association of Klinefelter's syndrome with an autoimmune disease found predominantly in women. The risk of SLE in men with Klinefelter's syndrome is predicted to be similar to the risk in normal women with 46,XX and approximately 14-fold higher than in men with 46,XY, consistent with the notion that SLE susceptibility is partly explained by an X chromosome gene-dose effect. FAU - Scofield, R Hal AU - Scofield RH AD - Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, and Oklahoma City VAMC, Oklahoma City, OK 73104, USA. hal-scofield@omrf.ouhsc.edu FAU - Bruner, Gail R AU - Bruner GR FAU - Namjou, Bahram AU - Namjou B FAU - Kimberly, Robert P AU - Kimberly RP FAU - Ramsey-Goldman, Rosalind AU - Ramsey-Goldman R FAU - Petri, Michelle AU - Petri M FAU - Reveille, John D AU - Reveille JD FAU - Alarcon, Graciela S AU - Alarcon GS FAU - Vila, Luis M AU - Vila LM FAU - Reid, Jeff AU - Reid J FAU - Harris, Bryan AU - Harris B FAU - Li, Shibo AU - Li S FAU - Kelly, Jennifer A AU - Kelly JA FAU - Harley, John B AU - Harley JB LA - eng GR - C06 RR 14570-01/RR/NCRR NIH HHS/United States GR - AR 049084/AR/NIAMS NIH HHS/United States GR - P30 AR053483/AR/NIAMS NIH HHS/United States GR - R01 AR043727-11/AR/NIAMS NIH HHS/United States GR - RR 020143/RR/NCRR NIH HHS/United States GR - R01 AR043727/AR/NIAMS NIH HHS/United States GR - R37 AI024717-21S1/AI/NIAID NIH HHS/United States GR - RR 015577/RR/NCRR NIH HHS/United States GR - AR 12253/AR/NIAMS NIH HHS/United States GR - R01 DE015223/DE/NIDCR NIH HHS/United States GR - AR 053734/AR/NIAMS NIH HHS/United States GR - R41 AI054117/AI/NIAID NIH HHS/United States GR - N01AR12253/AR/NIAMS NIH HHS/United States GR - P20 RR020143/RR/NCRR NIH HHS/United States GR - S10 RR019369/RR/NCRR NIH HHS/United States GR - AR 43727/AR/NIAMS NIH HHS/United States GR - AR 48940/AR/NIAMS NIH HHS/United States GR - R01 AI031584/AI/NIAID NIH HHS/United States GR - AR 24260/AR/NIAMS NIH HHS/United States GR - P20 RR015577/RR/NCRR NIH HHS/United States GR - AI 053747/AI/NIAID NIH HHS/United States GR - AI 24717/AI/NIAID NIH HHS/United States GR - UL1 RR025741/RR/NCRR NIH HHS/United States GR - N01 AR012253/AR/NIAMS NIH HHS/United States GR - M01 RR000048/RR/NCRR NIH HHS/United States GR - C06 RR014570/RR/NCRR NIH HHS/United States GR - M01 RR 00052/RR/NCRR NIH HHS/United States GR - RR 019369/RR/NCRR NIH HHS/United States GR - N01 AR062277/AR/NIAMS NIH HHS/United States GR - AI 062629/AI/NIAID NIH HHS/United States GR - AR 049743/AR/NIAMS NIH HHS/United States GR - R01 AR053734-04/AR/NIAMS NIH HHS/United States GR - AI 54117/AI/NIAID NIH HHS/United States GR - U19 AI062629/AI/NIAID NIH HHS/United States GR - R37 AI024717/AI/NIAID NIH HHS/United States GR - M01 RR014467/RR/NCRR NIH HHS/United States GR - M01 RR 014467/RR/NCRR NIH HHS/United States GR - R01 AI024717/AI/NIAID NIH HHS/United States GR - M01 RR000052/RR/NCRR NIH HHS/United States GR - K24 AR049743/AR/NIAMS NIH HHS/United States GR - I01 BX001451/BX/BLRD VA/United States GR - AI 31584/AI/NIAID NIH HHS/United States GR - M01 RR 00048/RR/NCRR NIH HHS/United States GR - P50 AR048940/AR/NIAMS NIH HHS/United States GR - R01 AR053734/AR/NIAMS NIH HHS/United States GR - DE 015223/DE/NIDCR NIH HHS/United States GR - R21 AI053747/AI/NIAID NIH HHS/United States GR - K24 AR049743-05/AR/NIAMS NIH HHS/United States GR - P01 AR049084/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Arthritis Rheum JT - Arthritis and rheumatism JID - 0370605 SB - IM MH - Case-Control Studies MH - Chromosomes, Human, X/*genetics MH - Female MH - Gene Dosage/*genetics MH - Genetic Predisposition to Disease MH - Genotype MH - Humans MH - Karyotyping MH - Klinefelter Syndrome/*genetics MH - Lupus Erythematosus, Systemic/*genetics MH - Male MH - Pedigree MH - Prevalence PMC - PMC2824898 MID - NIHMS174244 EDAT- 2008/08/01 09:00 MHDA- 2008/09/19 09:00 PMCR- 2010/02/19 CRDT- 2008/08/01 09:00 PHST- 2008/08/01 09:00 [pubmed] PHST- 2008/09/19 09:00 [medline] PHST- 2008/08/01 09:00 [entrez] PHST- 2010/02/19 00:00 [pmc-release] AID - 10.1002/art.23701 [doi] PST - ppublish SO - Arthritis Rheum. 2008 Aug;58(8):2511-7. doi: 10.1002/art.23701.