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Despite their severity, these issues are under-investigated. This study examined their association with FXTAS stages and potential as markers of disease progression in\n                    <jats:bold>\n                      <jats:italic>FMR1<\/jats:italic>\n                    <\/jats:bold>\n                    premutation (PM) carriers. A secondary analysis of Genotype-Phenotype cohort data (2017\u20132025, MIND Institute, UC Davis) examined swallowing\/choking problems, FXTAS stage, neuroimaging, and psychological distress (Symptom Checklist-90-Revised; SCL-90-R). Associations between independent and dependent variables were tested using Generalized Estimating Equation (GEE) regression due to their correlated data. The study included 169 PM carriers (mean age 65\u2009\u00b1\u200910.9 years; 54% male), with approximately 35% reporting swallowing\/choking difficulties. After adjusting for age and sex, individuals in the severe stage of FXTAS (stage 4\u20135) had a significantly higher risk of swallowing\/choking problems compared to those without FXTAS (adjusted odds ratio [aOR]\u2009=\u20094.17; 95%CI\u2009=\u20091.28\u201313.58). PM carriers with swallowing\/choking problems showed a significantly increased association with magnetic resonance imaging (MRI) findings of moderate to severe abnormalities in several brain regions, including cerebral atrophy (aOR\u2009=\u20092.69,\n                    <jats:bold>\n                      <jats:italic>p<\/jats:italic>\n                    <\/jats:bold>\n                    \u2009=\u20090.027), cerebellar atrophy (aOR\u2009=\u20093.34,\n                    <jats:bold>\n                      <jats:italic>p<\/jats:italic>\n                    <\/jats:bold>\n                    \u2009=\u20090.013), cerebellar white matter hyperintensity (aOR\u2009=\u20093.33,\n                    <jats:bold>\n                      <jats:italic>p<\/jats:italic>\n                    <\/jats:bold>\n                    \u2009=\u20090.012), and pons white matter hyperintensity (aOR\u2009=\u20093.93,\n                    <jats:bold>\n                      <jats:italic>p<\/jats:italic>\n                    <\/jats:bold>\n                    \u2009=\u20090.035). Swallowing\/choking problems are common in FXTAS, particularly in later stages, and may represent an important clinical marker of disease progression. These patients should be referred to speech-language pathologists for evaluation and treatment. Such interventions could reduce morbidity-mortality associated with these problems.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-25959-5","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:22:20Z","timestamp":1764163340000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Swallowing and choking difficulties as potential markers of FXTAS progression in FMR1 premutation carriers"],"prefix":"10.1038","volume":"15","author":[{"given":"Narueporn","family":"Likhitweerawong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica Alice Maria","family":"Montanaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellery R.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Yi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waralee","family":"Dejputtawat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udayakumar","family":"Narasimhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Klusek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nell","family":"Maltman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Tassone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randi J.","family":"Hagerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"25959_CR1","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/gim.2013.61","volume":"15","author":"KG Monaghan","year":"2013","unstructured":"Monaghan, K. 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The sponsors had no role in the design, execution, interpretation, or writing of the study. The other authors declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"42164"}}