{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:39:38Z","timestamp":1773052778321,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,9,18]],"date-time":"2015-09-18T00:00:00Z","timestamp":1442534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Nervous and Mental Disorders from the Ministry of Health, Labor, and Welfare, Japan"},{"name":"Japan Science and Technology Agency and the Ministry of Education, Culture, Sports, Science, and Technology, Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To clarify the potential association of copy number variations (CNVs) with multiple sclerosis (MS) and neuromyelitis optica (NMO) in Japanese cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genome\u2010wide association analyses of CNVs among 277 MS patients, 135 NMO\/NMO spectrum disorder (NMOSD) patients, and 288 healthy individuals as a discovery cohort, and among 296 MS patients, 76 NMO\/NMOSD patients, and 790 healthy individuals as a replication cohort were performed using high\u2010density single nucleotide polymorphism microarrays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A series of discovery and replication studies revealed that most identified CNVs were 5 to 50kb deletions at particular T cell receptor (TCR) gamma and alpha loci regions. Among these CNVs, a TCR gamma locus deletion was found in 16.40% of MS patients (<jats:italic>p<\/jats:italic>\u2009=\u20092.44E\u201040, odds ratio [OR]\u2009=\u200952.6), and deletion at the TCR alpha locus was found in 17.28% of MS patients (<jats:italic>p<\/jats:italic>\u2009=\u20091.70E\u201031, OR\u2009=\u200913.0) and 13.27% of NMO\/NMOSD patients (<jats:italic>p<\/jats:italic>\u2009=\u20095.79E\u201020, OR\u2009=\u200954.6). These CNVs were observed in peripheral blood T\u2010cell subsets only, suggesting the CNVs were somatically acquired. NMO\/NMOSD patients carrying the CNV tended to be seronegative for anti\u2013aquaporin\u20104 antibody or had significantly lower titers than those without CNV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Deletion\u2010type CNVs at specific TCR loci regions contribute to MS and NMO susceptibility. 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