{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:35:54Z","timestamp":1791250554390,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,8,20]],"date-time":"2014-08-20T00:00:00Z","timestamp":1408492800000},"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":[[2014,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recessive DYT16 dystonia associated with mutations in <jats:italic>PRKRA<\/jats:italic> has until now been reported only in seven Brazilian patients. The aim of this study was to elucidate the genetic cause underlying disease in a Polish family with autosomal\u2010recessive, early\u2010onset generalized dystonia and slight parkinsonism, and to explore further the role of <jats:italic>PRKRA<\/jats:italic> in a dystonia series of European ancestry. We employed whole\u2010exome sequencing in two affected siblings of the Polish family and filtered for rare homozygous and compound heterozygous variants shared by both exomes. Validation of the identified variants as well as homozygosity screening and copy number variation analysis was carried out in the two affected individuals and their healthy siblings. <jats:italic>PRKRA<\/jats:italic> was analyzed in 339 German patients with various forms of dystonia and 376 population\u2010based controls by direct sequencing or high\u2010resolution melting. The previously described homozygous p.Pro222Leu mutation in <jats:italic>PRKRA<\/jats:italic> was found to segregate with the disease in the studied family, contained in a 1.2 Mb homozygous region identical by state with all Brazilian patients in chromosome 2q31.2. The clinical presentation with young\u2010onset, progressive generalized dystonia and mild parkinsonism resembled the phenotype of the original DYT16 cases. <jats:italic>PRKRA<\/jats:italic> mutational screening in additional dystonia samples revealed three novel heterozygous changes (p.Thr34Ser, p.Asn102Ser, c.\u221214A&gt;G), each in a single subject with focal\/segmental dystonia. Our study provides the first independent replication of the DYT16 locus at 2q31.2 and strongly confirms the causal contribution of the <jats:italic>PRKRA<\/jats:italic> gene to DYT16. Our data suggest worldwide involvement of <jats:italic>PRKRA<\/jats:italic> in dystonia. \u00a9 2014 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.25981","type":"journal-article","created":{"date-parts":[[2014,8,20]],"date-time":"2014-08-20T11:42:26Z","timestamp":1408534946000},"page":"1504-1510","source":"Crossref","is-referenced-by-count":53,"title":["DYT16 revisited: Exome sequencing identifies <i>PRKRA<\/i> mutations in a European dystonia family"],"prefix":"10.1002","volume":"29","author":[{"given":"Michael","family":"Zech","sequence":"first","affiliation":[{"name":"Neurologische Klinik und Poliklinik, Klinikum rechts der Isar Technische Universit\u00e4t M\u00fcnchen Munich Germany"},{"name":"Institut f\u00fcr Humangenetik Helmholtz Zentrum M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Castrop","sequence":"additional","affiliation":[{"name":"Neurologische Klinik und Poliklinik, Klinikum rechts der Isar Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Schormair","sequence":"additional","affiliation":[{"name":"Neurologische Klinik und Poliklinik, Klinikum rechts der Isar Technische Universit\u00e4t M\u00fcnchen Munich Germany"},{"name":"Institut f\u00fcr Humangenetik Helmholtz Zentrum M\u00fcnchen Munich Germany"},{"name":"Institut f\u00fcr Humangenetik, Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Jochim","sequence":"additional","affiliation":[{"name":"Neurologische Klinik und Poliklinik, Klinikum rechts der Isar Technische Universit\u00e4t 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":"Nadine","family":"Gross","sequence":"additional","affiliation":[{"name":"Neurologische Klinik und Poliklinik, Klinikum rechts der Isar Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lichtner","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik Helmholtz Zentrum M\u00fcnchen Munich Germany"},{"name":"Institut f\u00fcr Humangenetik, Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Peters","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology II, Helmholtz Zentrum M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gieger","sequence":"additional","affiliation":[{"name":"Institute of Genetic Epidemiology, Helmholtz Zentrum M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Meitinger","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik Helmholtz Zentrum M\u00fcnchen Munich Germany"},{"name":"Institut f\u00fcr Humangenetik, Technische Universit\u00e4t M\u00fcnchen Munich Germany"},{"name":"Munich Cluster for Systems Neurology SyNergy Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim M.","family":"Strom","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik Helmholtz Zentrum M\u00fcnchen Munich Germany"},{"name":"Institut f\u00fcr Humangenetik, Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Oexle","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik Helmholtz Zentrum M\u00fcnchen Munich Germany"},{"name":"Institut f\u00fcr Humangenetik, Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Haslinger","sequence":"additional","affiliation":[{"name":"Neurologische Klinik und Poliklinik, Klinikum rechts der Isar Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Winkelmann","sequence":"additional","affiliation":[{"name":"Neurologische Klinik und Poliklinik, Klinikum rechts der Isar Technische Universit\u00e4t M\u00fcnchen Munich Germany"},{"name":"Institut f\u00fcr Humangenetik Helmholtz Zentrum M\u00fcnchen Munich Germany"},{"name":"Institut f\u00fcr Humangenetik, Technische Universit\u00e4t M\u00fcnchen Munich Germany"},{"name":"Munich Cluster for Systems Neurology SyNergy Munich Germany"},{"name":"Department of Neurology and Neurological Sciences and Center for Sleep Sciences and Medicine Stanford University School of Medicine Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt138"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70232-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.12.012"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70022-X"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-302841"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70075-9"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22632"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-009-5426-6"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25715"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21004"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890310012797"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws102"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a6ca62"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53221.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.35.1.73"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70117-0"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25647"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70174-6"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507360102"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24152"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2004.07.005"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318196cd7c"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2011.00520.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600942"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-011-8211-3"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmds.25981","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.25981","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T11:26:44Z","timestamp":1760959604000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.25981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,20]]},"references-count":26,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1002\/mds.25981"],"URL":"https:\/\/doi.org\/10.1002\/mds.25981","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,20]]}}}