{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:31:38Z","timestamp":1791207098545,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,12,6]],"date-time":"2012-12-06T00:00:00Z","timestamp":1354752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">FUS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TLS<\/jats:styled-content><\/jats:italic> have been associated with amyotrophic lateral sclerosis (ALS) in a few percent of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We screened 184 familial (FALS) and 200 sporadic <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>erman patients with ALS for <jats:italic><jats:styled-content style=\"fixed-case\">FUS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TLS<\/jats:styled-content><\/jats:italic> mutations by sequence analysis of exons 5, 6 and 13\u201315. We compared the phenotypes of patients with different <jats:italic><jats:styled-content style=\"fixed-case\">FUS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TLS<\/jats:styled-content><\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified three missense mutations p.<jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>510<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>, p.<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>514<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>, p.<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>521<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>, and the two truncating mutations p.<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>495<jats:styled-content style=\"fixed-case\">X<\/jats:styled-content> and p.<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>478Lfs<jats:styled-content style=\"fixed-case\">X<\/jats:styled-content>23 in samples from eight pedigrees. Both truncating mutations were associated with young onset and very aggressive disease courses, whereas the p.<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>521<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>, p.<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>514<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content> and in particular the p.<jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>510<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content> mutation showed a milder phenotype with disease durations ranging from 3\u2005years to more than 26\u2005years, the longest reported for a patient with a <jats:italic><jats:styled-content style=\"fixed-case\">FUS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TLS<\/jats:styled-content><\/jats:italic> mutation. Also, in a pair of monozygous twins with the p.<jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>510<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content> mutation, a remarkable similar disease course was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Mutations in <jats:italic><jats:styled-content style=\"fixed-case\">FUS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TLS<\/jats:styled-content><\/jats:italic> account for 8.7% (16 of 184) of <jats:styled-content style=\"fixed-case\">FALS<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>ermany. This is a higher prevalence than reported from other countries. Truncating <jats:italic><jats:styled-content style=\"fixed-case\">FUS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TLS<\/jats:styled-content><\/jats:italic> mutations result in a more severe phenotype than most missense mutations. The wide phenotypic differences have implications for genetic counselling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.12031","type":"journal-article","created":{"date-parts":[[2012,12,6]],"date-time":"2012-12-06T09:41:27Z","timestamp":1354786887000},"page":"540-546","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Truncating mutations in <i><scp>FUS<\/scp>\/<scp>TLS<\/scp><\/i> give rise to a more aggressive <scp>ALS<\/scp>\u2010phenotype than missense mutations: a clinico\u2010genetic study in <scp>G<\/scp>ermany"],"prefix":"10.1111","volume":"20","author":[{"given":"S.","family":"Waibel","sequence":"first","affiliation":[{"name":"Department of Neurology University of Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Neumann","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology University Hospital of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Rosenbohm","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Birve","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience Ume\u00e5 University Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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