{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:04:14Z","timestamp":1790964254059,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,2,5]],"date-time":"2014-02-05T00:00:00Z","timestamp":1391558400000},"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":[[2014,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>A founder mutation in the Thanatos\u2010associated (THAP) domain containing, apoptosis associated protein 1 (<jats:italic>THAP1<\/jats:italic>) gene causing primary dystonia was originally described in the Amish\u2010Mennonites. However, there may be both genotypic and phenotypic heterogeneity of dystonia in this population that may also inform studies in other ethnic groups. Genotyping for <jats:italic>THAP1<\/jats:italic> and for guanine nucleotide binding protein (G protein), \u03b1\u2010activating activity polypeptide, olfactory type (<jats:italic>GNAL<\/jats:italic>) mutations and genotype\u2010phenotype comparisons were performed for 76 individuals of Amish\u2010Mennonites heritage with primary dystonia. Twenty\u2010seven individuals had mutations in <jats:italic>THAP1<\/jats:italic>\u2014most with the founder indel mutation\u2014but two had different <jats:italic>THAP1<\/jats:italic> mutations, 8 had mutations in <jats:italic>GNAL<\/jats:italic>, and 1 had a de novo GAG deletion in torsin 1A (<jats:italic>TOR1A<\/jats:italic>) (dystonia 1 [<jats:italic>DYT1<\/jats:italic>]). In the primary analysis comparing <jats:italic>THAP1<\/jats:italic> carriers versus all non\u2010<jats:italic>THAP1<\/jats:italic>, non\u2010<jats:italic>GNAL<\/jats:italic>, non\u2010<jats:italic>TOR1A<\/jats:italic> individuals, age at onset was lower in <jats:italic>THAP1<\/jats:italic> carriers (mean age \u00b1 standard deviation, 15.5 \u00b1 9.2 years [range, 5\u201038 years] vs. 39.2 \u00b1 17.7 years [range, 1\u201070 years]; <jats:italic>P<\/jats:italic> &lt; 0.001), and <jats:italic>THAP1<\/jats:italic> carriers were more likely to have onset of dystonia in an arm (44.4% vs. 15.0%; <jats:italic>P<\/jats:italic> = 0.02) and to have arm involvement (88.9% vs. 22.5%; <jats:italic>P<\/jats:italic> &lt; 0.01), leg involvement (51.9% vs. 10.0%; <jats:italic>P<\/jats:italic> = 0.01), and jaw\/tongue involvement (33.3% vs. 7.5%; <jats:italic>P<\/jats:italic> = 0.02) involvement at their final examination. Carriers were less likely to have dystonia restricted to a single site (11.11% in carriers vs. 65.9% in noncarriers; <jats:italic>P<\/jats:italic> &lt; 0.01) and were less likely to have dystonia onset in cervical regions (25.9% of <jats:italic>THAP1<\/jats:italic> carriers vs. 52.5% of noncarriers; <jats:italic>P<\/jats:italic> = 0.04). Primary dystonia in the Amish\u2010Mennonites is genetically diverse and includes not only the <jats:italic>THAP1<\/jats:italic> indel founder mutation but also different mutations in <jats:italic>THAP1<\/jats:italic> and <jats:italic>GNAL<\/jats:italic> as well as the <jats:italic>TOR1A<\/jats:italic> GAG deletion. Phenotype, particularly age at onset combined with final distribution, may be highly specific for the genetic etiology. \u00a9 2014 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.25818","type":"journal-article","created":{"date-parts":[[2014,2,5]],"date-time":"2014-02-05T19:31:39Z","timestamp":1391628699000},"page":"812-818","source":"Crossref","is-referenced-by-count":38,"title":["Heterogeneity in primary dystonia: Lessons from <i>THAP1<\/i>, <i>GNAL<\/i>, and <i>TOR1A<\/i> in Amish\u2010Mennonites"],"prefix":"10.1002","volume":"29","author":[{"given":"Rachel","family":"Saunders\u2010Pullman","sequence":"first","affiliation":[{"name":"Department of Neurology Beth Israel Medical Center New York New York USA"},{"name":"Department of Neurology Albert Einstein College of Medicine Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"San Luciano","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California\u2010San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Raymond","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Brashear","sequence":"additional","affiliation":[{"name":"Department of Neurology Wake Forest School of Medicine Winston Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Ortega","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Deik","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie J.","family":"Ozelius","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York New York USA"},{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan B.","family":"Bressman","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Medical Center New York New York USA"},{"name":"Department of Neurology Albert Einstein College of Medicine Bronx New York 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