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This study focuses on genes linked to the VD signaling pathway in families with MS. The evaluation of gene variants in all the members of families could contribute to an additional knowledge on the information obtained from case\u2010control studies that use nonrelated healthy people.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>We studied 94 individuals from 15 families including at least two patients with MS. We performed whole\u2010exome next generation sequencing on all individuals and analyzed variants of the <jats:italic>DHCR7<\/jats:italic>, <jats:italic>CYP2R1<\/jats:italic>, <jats:italic>CYP3A4<\/jats:italic>, <jats:italic>CYP27A1<\/jats:italic>, <jats:italic>GC<\/jats:italic>, <jats:italic>CYP27B1<\/jats:italic>, <jats:italic>LRP2<\/jats:italic>, <jats:italic>CUBN<\/jats:italic>, <jats:italic>DAB2<\/jats:italic>, <jats:italic>FCGR<\/jats:italic>, <jats:italic>RXR<\/jats:italic>, <jats:italic>VDR<\/jats:italic>, <jats:italic>CYP24A1,<\/jats:italic> and <jats:italic>PDIA3<\/jats:italic> genes. We also studied <jats:italic>PTH<\/jats:italic>, <jats:italic>FGF23<\/jats:italic>, <jats:italic>METTL1<\/jats:italic>, <jats:italic>METTL21B,<\/jats:italic> and the role of the linkage disequilibrium block on the long arm of chromosome 12, through analysis of the <jats:italic>CDK4<\/jats:italic>, <jats:italic>TSFM<\/jats:italic>, <jats:italic>AGAP2<\/jats:italic>, and <jats:italic>AVIL<\/jats:italic> genes. We compared patients with MS, other AIDs and unaffected members from different family types.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study described the variants in the VD signaling pathway that appear in families with at least two patients with MS. Some infrequent variants were detected in these families, but no significant difference was observed between patients with MS and\/or other AIDs and unaffected family members in the frequency of these variants. Variants previously associated with MS in the literature were not observed in these families or were distributed similarly in patients and unaffected family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The study of genes involved in the VD signaling pathway in families that include more than one patient with MS did not identify any variants that could explain the presence of the disease, suggesting that VD metabolism could probably play a role in MS more as an environmental factor rather than as a genetic factor. Our study also supports the analysis of cases and unaffected individuals within families in order to determine the influence of genetic factors.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.1272","type":"journal-article","created":{"date-parts":[[2019,3,22]],"date-time":"2019-03-22T02:29:08Z","timestamp":1553221748000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Exonic variants of genes related to the vitamin D signaling pathway in the families of familial multiple sclerosis using whole\u2010exome next generation sequencing"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2518-338X","authenticated-orcid":false,"given":"Vanesa","family":"Pytel","sequence":"first","affiliation":[{"name":"Department of Neurology, Institute of Neurosciences, IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"},{"name":"Laboratory of Neurobiology, Institute of Neurosciences, IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi A.","family":"Mat\u00edas\u2010Guiu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Neurosciences, IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Torre\u2010Fuentes","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Institute of Neurosciences, IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Montero\u2010Escribano","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Neurosciences, IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Maietta","sequence":"additional","affiliation":[{"name":"Nimgenetics Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Botet","sequence":"additional","affiliation":[{"name":"Nimgenetics Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Nimgenetics Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulises","family":"G\u00f3mez\u2010Pinedo","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Institute of Neurosciences, IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Mat\u00edas\u2010Guiu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Neurosciences, IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"},{"name":"Laboratory of Neurobiology, Institute of Neurosciences, IdISSC, Hospital Cl\u00ednico San Carlos Universidad Complutense de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10528-016-9783-4"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-018-1152-9"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq155"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-101085"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2011.81"},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"e0144565","DOI":"10.1371\/journal.pone.0144565","article-title":"The association of vitamin D receptor polymorphisms with multiple sclerosis in a case\u2010control study from Kuwait","volume":"10","author":"Altemaimi R. 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