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Each disease is caused by a complex combination of genetic and environmental variables, many involving an autoimmune response. Even though these conditions are fundamentally similar, research into genetic factors, their unique clinical manifestations, and lesion pathology has helped with differential diagnosis and disease pathogenesis knowledge. This review aims to synthesize the genetic approaches that explain the differential susceptibility between these diseases, explore the overlapping clinical features, and pathological findings, discuss existing and emerging hypotheses on the etiology of demyelination, and assess recent pathogenicity studies and their implications for human demyelination. This review presents critical information from previous studies on the disease, which asks several questions to understand the gaps in research in this field.<\/jats:p>","DOI":"10.3390\/genes14071319","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T02:05:02Z","timestamp":1687745102000},"page":"1319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Genetic Basis of Inflammatory Demyelinating Diseases of the Central Nervous System: Multiple Sclerosis and Neuromyelitis Optica Spectrum"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7054-3313","authenticated-orcid":false,"given":"Genaro Gabriel","family":"Ortiz","sequence":"first","affiliation":[{"name":"Department of Philosophical and Methodological Disciplines and Service of Molecular Biology in Medicine Hospital, Civil University Health Sciences Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Department of Neurology, High Specialty Medical Unit, Western National Medical Center of the Mexican Institute of Social Security, Guadalajara 44329, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2233-571X","authenticated-orcid":false,"given":"Blanca M. 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