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The genotype\u2013phenotype correlations and intergenerational instabilities related to (TTTCA)exp and (TTTTA)exp are still unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim was to investigate the genotype\u2013phenotype correlations and intergenerational instabilities related to (TTTCA)exp and (TTTTA)exp in FCMTE1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed targeted long\u2010read sequencing on 77 FCMTE1 patients. After quality control, metrics such as total repeat count, respective (TTTTA)exp and (TTTCA)exp count, and interruptions were assessed in 73 patients. Correlations between metrics and the patients' clinical features, as well as repeat instability during parental transmission, were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 73 alleles, the average total repeat counts were 848\u2009\u00b1\u2009152\u2009units, with (TTTTA)exp and (TTTCA)exp averaging 498\u2009\u00b1\u2009196\u2009units and 356\u2009\u00b1\u2009110\u2009units, respectively. (TTTCA)exp counts were inversely correlated with the age at onset for cortical tremor (Spearman's rho\u2009=\u2009\u22120.348, <jats:italic>P<\/jats:italic>\u2009=\u20090.005) and epilepsy (Spearman's rho\u2009=\u2009\u22120.424, <jats:italic>P<\/jats:italic>\u2009=\u20090.003). A negative correlation was found between (TTTCA)exp counts and relatively moderate seizure pattern with prodrome (odds ratio\u2009=\u20090.988, 95% confidence interval: 0.980\u20130.995, <jats:italic>P<\/jats:italic>\u2009=\u20090.002). During parental transmission, (TTTCA)exp counts increased significantly (<jats:italic>P<\/jats:italic>\u2009=\u20090.007), with maternal transmission showing a significantly larger increase compared to paternal transmission (<jats:italic>P<\/jats:italic>\u2009=\u20090.013).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The (TTTCA)exp insertion serves as the length\u2010dependent pathogenic component within the two\u2010motif repeat expansion. Its differential expanding nature during parental transmissions is highly associated with the genetic anticipation in FCMTE1. \u00a9 2024 International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.30057","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T07:59:27Z","timestamp":1732175967000},"page":"315-323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["(<scp>TTTCA<\/scp>)exp Drives the Genotype\u2013Phenotype Correlation and Genetic Anticipation in <scp>FCMTE1<\/scp>"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9940-9327","authenticated-orcid":false,"given":"Xinhui","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibin","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7677-8930","authenticated-orcid":false,"given":"Haotian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4129-9761","authenticated-orcid":false,"given":"Dehao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"Department of Neurology Zhuji Affiliated Hospital of Wenzhou Medical University  Zhuji China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huijun","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Huzhou Third Municipal Hospital  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiling","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lebo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8824-3370","authenticated-orcid":false,"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Taizhou Central Hospital (Taizhou University Hospital)  Taizhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aisi","family":"Fu","sequence":"additional","affiliation":[{"name":"Shanghai Dgensee Medical Technology Co., Ltd.  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