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However, type and frequency of neurological involvement are widely undetermined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We assessed clinical characteristics of 151 (108 with MS) patients carrying NLRP3-, MEFV- and TNFRSF1A low-penetrance variants\u00a0 from the Institute of Clinical Neuroimmunology. We evaluated demographic, genetic, and clinical features with a focus on central nervous system (CNS) involvement including magnetic resonance imaging (MRI) results and cerebrospinal fluid (CSF) data. The disease course of AID patients with MS was compared to a matched MS control group without mutations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The genetic distribution comprised 36 patients (23%) with NLRP3- and 66 patients (43%) with TNFRSF1A low-penetrance variants as well as 53 (34%) patients carrying pathogenic mutations or low-penetrance variants in the\n                      <jats:italic>MEFV<\/jats:italic>\n                      gene. MS patients displayed most frequently the R92Q TNFRSF1A variant (\n                      <jats:italic>n<\/jats:italic>\n                      = 51; 46%) followed by the Q703K NLRP3 variant (\n                      <jats:italic>n<\/jats:italic>\n                      = 15; 14%) and the E148Q substitution (\n                      <jats:italic>n<\/jats:italic>\n                      = 9; 8%) in the MEFV gene. The disease course of MS was not influenced by the genetic variants and did not differ from MS patients (\n                      <jats:italic>n<\/jats:italic>\n                      = 51) without mutations. AID patients without MS most frequently harbored MEFV mutations (\n                      <jats:italic>n<\/jats:italic>\n                      = 19, 43%) followed by NLRP3- (\n                      <jats:italic>n<\/jats:italic>\n                      = 17, 39%) and TNFRSF1A (\n                      <jats:italic>n<\/jats:italic>\n                      = 8, 18%) low-penetrance variants. Sixteen (36%) of them suffered from severe CNS involvement predominantly recurrent aseptic meningoencephalitis and optic neuritis accompanied by abnormal MRI and CSF results. Severe CNS inflammation was associated with the Q703K allele. Headache was a highly prevalent neurological symptom (up to 74%), irrespective of the underlying genetic variation. The NLRP3 cohort without MS more frequently exhibited affections of the cranial nerves (CN) (\n                      <jats:italic>p<\/jats:italic>\n                      =\n                      <jats:italic>0<\/jats:italic>\n                      .\n                      <jats:italic>0228<\/jats:italic>\n                      ) and motor symptoms (\n                      <jats:italic>p<\/jats:italic>\n                      =\n                      <jats:italic>0<\/jats:italic>\n                      .\n                      <jats:italic>0455<\/jats:italic>\n                      ). Elevated acute-phase reactants were detected in all patients, and fever episodes were present in up to 50%. Arthralgias were the most frequently identified constitutional symptom among all subgroups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data highlight the high prevalence of neurological manifestations, including concomitant MS, among NLRP3-, MEFV-, and TNFRSF1A low-penetrance variants. In particular, patients carrying the Q703K NLRP3 variant are at risk for severe CNS inflammation and CN affection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-020-01867-5","type":"journal-article","created":{"date-parts":[[2020,6,20]],"date-time":"2020-06-20T10:02:30Z","timestamp":1592647350000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Neurological phenotypes in patients with NLRP3-, MEFV-, and TNFRSF1A low-penetrance variants"],"prefix":"10.1186","volume":"17","author":[{"given":"Elisabeth","family":"Mulazzani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Havla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Schl\u00fcter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Meinl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa-Ann","family":"Gerdes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"K\u00fcmpfel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,20]]},"reference":[{"issue":"3","key":"1867_CR1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/ng756","volume":"29","author":"HM Hoffman","year":"2001","unstructured":"Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD. 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All participants gave written informed consent (project 159-03, 163-16 and 600-15).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"E. Mulazzani, D. Wagner, M. Schl\u00fcter, I. Meinl, and L.-A. Gerdes report no disclosures. J. Havla reports personal fees and non-financial support from Merck, Novartis, Roche, Santhera, Biogen, and Sanofi Genzyme and non-financial support of the Guthy-Jackson Charitable Foundation, all outside the submitted work.T. K\u00fcmpfel has received speaker honoraria including advisory boards from Bayer Healthcare, Teva Pharma, Merck, Novartis Pharma, Sanofi-Aventis\/Genzyme, Roche Pharma, and Biogen as well as grant support from Novartis and Chugai Pharma in the past.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"196"}}