{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:46:23Z","timestamp":1761007583009,"version":"build-2065373602"},"reference-count":59,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022431","name":"Medical Research Council Centre for Neurodevelopmental Disorders","doi-asserted-by":"publisher","award":["MR\/N028767\/1"],"award-info":[{"award-number":["MR\/N028767\/1"]}],"id":[{"id":"10.13039\/501100022431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004271","name":"Sapienza Universit\u00e0 di Roma","doi-asserted-by":"publisher","award":["2018\/2019 grants"],"award-info":[{"award-number":["2018\/2019 grants"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by an expanded GAA repeat in the first intron of the <jats:italic>FXN<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to analyze leukocyte telomeres length (LTL) in FRDA to verify the possible relationships between LTL and disease progression. We investigated LTL in a cohort of FRDA biallelic patients (n\u2009=\u200961), heterozygous (n\u2009=\u200929), and age\u2010matched healthy subjects (n\u2009=\u200987).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>LTL was measured by real\u2010time polymerase chain reaction quantitative analysis (qPCR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed that before 35\u2009years of age, leukocyte telomeres were longer in patients than in controls, whereas the reverse applies in patients above 36\u2009years of age. Interestingly, LTL was greater than controls at any age in heterozygous subjects. This picture mirrors what has been previously observed in vitro in FRDA cultured fibroblasts, showing significantly longer telomeres at early passages because of activation of an alternative lengthening of telomeres (ALT)\u2010like mechanism, but showing accelerated telomere shortening as population doubling increases. GAA1 repeat length is positively correlated with the LTL and negatively correlated with the age at blood sampling. The relationship of LTL with clinical parameters (cardiomyopathy, diabetes, dependence on a wheelchair) was also analyzed. Significantly shorter leukocyte telomeres were associated with the presence of cardiomyopathy, but not with diabetes and the dependence on a wheelchair.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, the present study indicates that telomere length analysis in FRDA may be a relevant biomarker for following the stages of the disease. \u00a9 2024 The Author(s). <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29976","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T12:06:18Z","timestamp":1725537978000},"page":"2058-2066","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unusual Age\u2010Dependent Behavior of Leukocytes Telomere Length in Friedreich's Ataxia"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5565-6379","authenticated-orcid":false,"given":"Daniela","family":"Scarabino","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology and Pathology National Research Council (CNR)  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liana","family":"Veneziano","sequence":"additional","affiliation":[{"name":"Institute of Translational Pharmacology National Research Council (CNR)  Rome Italy"},{"name":"Human Functional Genomics Laboratory IRCCS San Raffaele  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suran","family":"Nethisinghe","sequence":"additional","affiliation":[{"name":"Ataxia Centre, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology University College London  London United 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