{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:35:31Z","timestamp":1791250531419,"version":"4.1.0"},"reference-count":8,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,2,4]],"date-time":"2015-02-04T00:00:00Z","timestamp":1423008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Myoclonus\u2010dystonia (M\u2010D) is a hyperkinetic movement disorder with predominant myoclonic symptoms combined with dystonia of the upper part of the body. A proportion of M\u2010D cases are caused by mutations in the epsilon\u2010sarcoglycan gene. In remaining M\u2010D patients, no genetic factor has been established, indicating genetic heterogeneity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients were included in a prospective clinical database and recruited from referral centers and general neurology clinics in The Netherlands. To investigate new genetic causal factors in M\u2010D syndrome, we performed homozygosity mapping combined with exome sequencing in a three\u2010generation M\u2010D family and genetically screened 24 additional patients with M\u2010D.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found co\u2010segregation of the rare missense variant Thr1904Met in the <jats:italic>RELN<\/jats:italic> gene. By additional screening of an M\u2010D cohort, we identified co\u2010segregation of <jats:italic>RELN<\/jats:italic> variants in two families (Thr1904Met, Ile1217Met) and identified two sporadic <jats:italic>RELN<\/jats:italic> mutation carriers (Pro1703Arg, Leu411Ile). Taken together, five of 25 <jats:italic>SGCE<\/jats:italic>\u2010negative M\u2010D patients carried <jats:italic>RELN<\/jats:italic> rare missense variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We propose that <jats:italic>RELN<\/jats:italic> mutations contribute to the genetic heterogeneity of M\u2010D. Reelin is a large secreted glycoprotein that plays essential roles in the cytoarchitecture of laminated brain structures and modulation of synaptic transmission and plasticity. \u00a9 2015 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.26070","type":"journal-article","created":{"date-parts":[[2015,2,4]],"date-time":"2015-02-04T01:15:37Z","timestamp":1423012537000},"page":"415-419","source":"Crossref","is-referenced-by-count":26,"title":["<i>RELN<\/i> rare variants in myoclonus\u2010dystonia"],"prefix":"10.1002","volume":"30","author":[{"given":"Justus L.","family":"Groen","sequence":"first","affiliation":[{"name":"Department of Neurology Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"},{"name":"Department of Genome Analysis Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Ritz","sequence":"additional","affiliation":[{"name":"Department of Genome Analysis Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Jalalzadeh","sequence":"additional","affiliation":[{"name":"Department of Neurology Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra M.A.","family":"van der Salm","sequence":"additional","affiliation":[{"name":"Department of Neurology Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Jongejan","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology and Bio\u2010Statistics Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf R.","family":"Mook","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin A.","family":"Haagmans","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aeilko H.","family":"Zwinderman","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology and Bio\u2010Statistics Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdi M.","family":"Motazacker","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul C.","family":"Hennekam","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Baas","sequence":"additional","affiliation":[{"name":"Department of Genome Analysis Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina A.J.","family":"Tijssen","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Groningen  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,4]]},"reference":[{"key":"e_1_2_8_2_1","article-title":"CACNA1B mutation is linked to unique myoclonus\u2010dystonia syndrome","author":"Groen 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