{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T02:54:00Z","timestamp":1777604040583,"version":"3.51.4"},"reference-count":41,"publisher":"Cambridge University Press (CUP)","issue":"2","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Twin Res Hum Genet"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fragile X-associated tremor\/ataxia syndrome (FXTAS) occurs in carriers of fragile X mental retardation 1 (<jats:italic>FMR1<\/jats:italic>) X-linked small CGG expansion (gray zone [GZ] and premutation [PM]) alleles, containing 41\u2013200 repeats. Major features comprise kinetic tremor, gait ataxia, cognitive decline and cerebellar peduncular white matter lesions, but atypical\/incomplete FXTAS may occur. We explored the possibility of polygenic effects modifying the FXTAS spectrum phenotypes. We used three motor scales and selected cognitive tests in a series of three males and three females from a single sibship carrying PM or GZ alleles (44 to 75 repeats). The molecular profiles from these siblings were determined by genomewide association study with single-nucleotide polymorphism (SNP) genotyping by Illumina Global Screening Array. Nonparametric linkage analysis was applied and Parkinson\u2019s disease (PD) polygenic risk scores (PRSs) were calculated for all the siblings, based on 107 known risk variants. All male and female siblings manifested similar kinetic tremor phenotypes. In contrast to FXTAS, they showed negligible gait ataxia, and few white matter lesions on MRI. Cognitive functioning was unaffected. Suggestive evidence of linkage to a broad region of the short arm of chromosome 10 was obtained, and median PD PRS for the sibship fell within the top 30% of a sample of over 500,000 UK and Australian controls. The genomewide study results are suggestive of modifying effects of genetic risk loci linked to PD, on the neurological phenotype of FMR1-CGG small expansion carriers, resulting in an oligosymptomatic kinetic tremor seen in FXTAS spectrum, but also consistent with essential tremor.<\/jats:p>","DOI":"10.1017\/thg.2021.10","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T06:05:49Z","timestamp":1616565949000},"page":"95-102","source":"Crossref","is-referenced-by-count":10,"title":["\u2018Essential Tremor\u2019 Phenotype in FMR1 Premutation\/Gray Zone Sibling Series: Exploring Possible Genetic Modifiers"],"prefix":"10.1017","volume":"24","author":[{"given":"Danuta Z.","family":"Loesch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David L.","family":"Duffy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas G.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flora","family":"Tassone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Atkinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elsdon","family":"Storey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"S1832427421000104_ref12","doi-asserted-by":"publisher","DOI":"10.1038\/ng1005-1015"},{"key":"S1832427421000104_ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2015.02.015"},{"key":"S1832427421000104_ref4","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giz082"},{"key":"S1832427421000104_ref13","doi-asserted-by":"publisher","DOI":"10.1086\/386296"},{"key":"S1832427421000104_ref17","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-6-31"},{"key":"S1832427421000104_ref35","volume-title":"Symbol Digit Modalities Test","author":"Smith","year":"1982"},{"key":"S1832427421000104_ref27","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27420"},{"key":"S1832427421000104_ref10","first-page":"271","volume-title":"Parkinson\u2019s disease and movement disorders","author":"Fahn","year":"1993"},{"key":"S1832427421000104_ref9","first-page":"153","volume-title":"Recent developments in Parkinson\u2019s disease","author":"Fahn","year":"1987"},{"key":"S1832427421000104_ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2019.05.002"},{"key":"S1832427421000104_ref14","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70125-X"},{"key":"S1832427421000104_ref28","doi-asserted-by":"publisher","DOI":"10.1002\/gps.1610"},{"key":"S1832427421000104_ref32","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35833"},{"key":"S1832427421000104_ref29","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww242"},{"key":"S1832427421000104_ref33","volume-title":"The Halstead-Reitan Neuropsychological Test Battery","author":"Reitan","year":"1985"},{"key":"S1832427421000104_ref40","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.00135"},{"key":"S1832427421000104_ref37","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990528)84:3<250::AID-AJMG17>3.0.CO;2-4"},{"key":"S1832427421000104_ref39","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(96)00231-6"},{"key":"S1832427421000104_ref2","doi-asserted-by":"publisher","DOI":"10.1080\/13854049108403297"},{"key":"S1832427421000104_ref16","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23755"},{"key":"S1832427421000104_ref21","doi-asserted-by":"publisher","DOI":"10.1159\/000328866"},{"key":"S1832427421000104_ref26","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.577246"},{"key":"S1832427421000104_ref22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2005.00425.x"},{"key":"S1832427421000104_ref18","doi-asserted-by":"publisher","DOI":"10.5334\/tohm.112"},{"key":"S1832427421000104_ref19","doi-asserted-by":"publisher","DOI":"10.1086\/374321"},{"key":"S1832427421000104_ref30","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30320-5"},{"key":"S1832427421000104_ref23","first-page":"78","volume-title":"Tandem repeat polymorphisms: Genetic plasticity, neural diversity and disease","author":"Loesch","year":"2011"},{"key":"S1832427421000104_ref36","doi-asserted-by":"publisher","DOI":"10.5334\/tohm.441"},{"key":"S1832427421000104_ref7","volume-title":"SCL-90-R: Symptom Checklist-90-R. 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