{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:37:46Z","timestamp":1790660266160,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T00:00:00Z","timestamp":1687564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Individuals with telomere biology disorders (TBDs) have very short telomeres, high risk of bone marrow failure (BMF), and reduced survival. Using data from TBD patients, a mean leukocyte Southern blot telomere length (TL) of 5 kilobases (kb) was estimated as the \u2018telomere brink\u2019 at which human survival is markedly reduced. However, the shortest telomere, not the mean TL, signals replicative senescence. We used the Telomere Shortest Length Assay (TeSLA) to tally TL of all 46 chromosomes in blood\u2010derived DNA and examined its relationship with TBDs. Patients (<jats:italic>n<\/jats:italic>\u2009=\u200918) had much shorter mean TL (TeSmTL) (2.54\u2009\u00b1\u20090.41\u2009kb vs. 4.48\u2009\u00b1\u20090.52\u2009kb, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and more telomeres &lt;3\u2009kb than controls (<jats:italic>n<\/jats:italic>\u2009=\u200922) (70.43\u2009\u00b1\u20098.76% vs. 33.05\u2009\u00b1\u20096.93%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). The proportion of ultrashort telomeres (&lt;1.6\u2009kb) was also higher in patients than controls (39.29\u2009\u00b1\u200910.69% vs. 10.40\u2009\u00b1\u20094.09%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). TeS &lt;1.6\u2009kb was associated with severe (<jats:italic>n<\/jats:italic>\u2009=\u200911) compared with non\u2010severe (<jats:italic>n<\/jats:italic>\u2009=\u20097) BMF (<jats:italic>p<\/jats:italic>\u2009=\u20090.027). Patients with multi\u2010organ manifestations (<jats:italic>n<\/jats:italic>\u2009=\u200910) had more telomeres &lt;1.6\u2009kb than those with one affected organ system (<jats:italic>n<\/jats:italic>\u2009=\u20098) (<jats:italic>p<\/jats:italic>\u2009=\u20090.029). Findings suggest that TBD clinical manifestations are associated with a disproportionately higher number of haematopoietic cell telomeres reaching a telomere brink, whose length at the single telomere level is yet to be determined.<\/jats:p>","DOI":"10.1111\/bjh.18945","type":"journal-article","created":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T01:35:47Z","timestamp":1687656947000},"page":"820-828","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The distribution and accumulation of the shortest telomeres in telomere biology disorders"],"prefix":"10.1111","volume":"203","author":[{"given":"Hannah A.","family":"Raj","sequence":"first","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch National Cancer Institute  Rockville Maryland 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