Identification of Adult Patients With Classical Dyskeratosis Congenita or Cryptic Telomere Biology Disorder by Telomere Length Screening Using Age-modified Criteria.
Journal
HemaSphere
ISSN: 2572-9241
Titre abrégé: Hemasphere
Pays: United States
ID NLM: 101740619
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
received:
12
09
2022
accepted:
08
03
2023
medline:
25
4
2023
pubmed:
25
4
2023
entrez:
25
04
2023
Statut:
epublish
Résumé
Telomere biology disorders (TBD) result from premature telomere shortening due to pathogenic germline variants in telomere maintenance-associated genes. In adults, TBD are characterized by mono/oligosymptomatic clinical manifestations (cryptic TBD) contributing to severe underdiagnosis. We present a prospective multi-institutional cohort study where telomere length (TL) screening was performed in either newly diagnosed patients with aplastic anemia (AA) or if TBD was clinically suspected by the treating physician. TL of 262 samples was measured via flow-fluorescence in situ hybridization (FISH). TL was considered suspicious once below the 10th percentile of normal individuals (standard screening) or if below 6.5 kb in patients >40 years (extended screening). In cases with shortened TL, next generation sequencing (NGS) for TBD-associated genes was performed. The patients referred fell into 6 different screening categories: (1) AA/paroxysmal nocturnal hemoglobinuria, (2) unexplained cytopenia, (3) dyskeratosis congenita, (4) myelodysplastic syndrome/acute myeloid leukemia, (5) interstitial lung disease, and (6) others. Overall, TL was found to be shortened in 120 patients (n = 86 standard and n = 34 extended screening). In 17 of the 76 (22.4%) standard patients with sufficient material for NGS, a pathogenic/likely pathogenic TBD-associated gene variant was identified. Variants of uncertain significance were detected in 17 of 76 (22.4%) standard and 6 of 29 (20.7%) extended screened patients. Expectedly, mutations were mainly found in
Identifiants
pubmed: 37096215
doi: 10.1097/HS9.0000000000000874
pmc: PMC10121438
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e874Informations de copyright
Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.
Déclaration de conflit d'intérêts
THB and FB have a long-ranging scientific collaboration with Repeat Dx., Vancouver, Canada. All the other authors have no conflicts of interest to disclose.
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