{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:43:28Z","timestamp":1792089808574,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,9,26]],"date-time":"2016-09-26T00:00:00Z","timestamp":1474848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dystonia is clinically and genetically heterogeneous. Despite being a first\u2010line testing tool for heterogeneous inherited disorders, whole\u2010exome sequencing has not yet been evaluated in dystonia diagnostics. We set up a pilot study to address the yield of whole\u2010exome sequencing for early\u2010onset generalized dystonia, a disease subtype enriched for monogenic causation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical whole\u2010exome sequencing coupled with bioinformatics analysis and detailed phenotyping of mutation carriers was performed on 16 consecutive cases with genetically undefined early\u2010onset generalized dystonia. Candidate pathogenic variants were validated and tested for cosegregation. The whole\u2010exome approach was complemented by analyzing 2 mutated yet unestablished causative genes in another 590 dystonia cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Whole\u2010exome sequencing detected clinically relevant mutations of known dystonia\u2010related genes in 6 generalized dystonia cases (37.5%), among whom 3 had novel variants. Reflecting locus heterogeneity, identified unique variants were distributed over 5 genes (\n                      <jats:italic>GCH1, THAP1, TOR1A, ANO3, ADCY5<\/jats:italic>\n                      ), of which only 1 (\n                      <jats:italic>ANO3<\/jats:italic>\n                      ) was mutated recurrently. Three genes (\n                      <jats:italic>GCH1, THAP1, TOR1A<\/jats:italic>\n                      ) were associated with isolated generalized dystonia, whereas 2 (\n                      <jats:italic>ANO3, ADCY5<\/jats:italic>\n                      ) gave rise to combined dystonia\u2010myoclonus phenotypes. Follow\u2010up screening of\n                      <jats:italic>ANO3<\/jats:italic>\n                      and\n                      <jats:italic>ADCY5<\/jats:italic>\n                      revealed a set of distinct variants of interest, the pathogenicity of which was supported by bioinformatics testing and cosegregation work.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study identified whole\u2010exome sequencing as an effective strategy for molecular diagnosis of early\u2010onset generalized dystonia and offers insights into the heterogeneous genetic architecture of this condition. Furthermore, it provides confirmatory evidence for a dystonia\u2010relevant role of\n                      <jats:italic>ANO3<\/jats:italic>\n                      and\n                      <jats:italic>ADCY5<\/jats:italic>\n                      , both of which likely associate with a broader spectrum of dystonic expressions than previously thought. \u00a9 2016 International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.26808","type":"journal-article","created":{"date-parts":[[2016,9,26]],"date-time":"2016-09-26T04:38:13Z","timestamp":1474864693000},"page":"549-559","source":"Crossref","is-referenced-by-count":98,"title":["Clinical exome sequencing in early\u2010onset generalized dystonia and large\u2010scale resequencing follow\u2010up"],"prefix":"10.1002","volume":"32","author":[{"given":"Michael","family":"Zech","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Neurogenomik Helmholtz Zentrum M\u00fcnchen Munich Germany"},{"name":"Klinik und Poliklinik f\u00fcr Neurologie, Klinikum rechts der lsar, Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Boesch","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University Innsbruck Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Jochim","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Neurologie, Klinikum rechts der lsar, Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrina","family":"Weber","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Neurogenomik Helmholtz Zentrum M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Meindl","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Neurologie, Klinikum rechts der lsar, Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Schormair","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Neurogenomik Helmholtz Zentrum M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wieland","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik, Helmholtz Zentrum M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lunetta","sequence":"additional","affiliation":[{"name":"Neuromuscular Omnicentre Sud (NEMO SUD), Fondazione Aurora Onlus Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Sansone","sequence":"additional","affiliation":[{"name":"Neuromuscular Omnicentre (NEMO), Fondazione Serena Onlus Milan 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