High-throughput STELA provides a rapid test for the diagnosis of telomere biology disorders

• DOI: 10.1007/s00439-021-02257-4
• Publication Date: 2021-03-11T19:02:45Z
• Authors: Kevin Norris; Amanda J. Walne; Mark J. Ponsford; Kez Cleal; Julia W. Grimstead; Alicia Ellison; Jenna Alnajar; Inderjeet Dokal; Tom Vulliamy; Duncan M. Baird
• Keywords: Adult; Male; Heterozygote; 0303 health sciences; Fetal Growth Retardation; Adolescent; Genetic Carrier Screening; Age Factors; Infant; Bone Marrow Failure Disorders; Middle Aged; Dyskeratosis Congenita; 3. Good health; 03 medical and health sciences; Case-Control Studies; Child, Preschool; Intellectual Disability; Asymptomatic Diseases; Microcephaly; Humans; Female; Child; Original Investigation; Aged

Abstract Telomere biology disorders are complex clinical conditions that arise due to mutations in genes required for telomere maintenance. length has been utilised as part of the diagnostic work-up patients with these diseases; here, we have tested utility high-throughput STELA (HT-STELA) this purpose. HT-STELA was applied a cohort unaffected individuals ( n = 171) and retrospective mutation carriers 172). displayed low measurement error inter- intra-assay coefficient variance 2.3% 1.8%, respectively. Whilst declined function age, appeared increase preponderance shorter telomeres detected younger (< 20 years age). These were more severely affected, age-adjusted differentials could be used stratify overall survival (Hazard Ratio 5.6 (1.5–20.5); p < 0.0001). lengths asymptomatic than controls 0.0001), but longer symptomatic 0.0001) heterogeneity dependent on diagnosis mutational status. Our data show ability detect short lengths, not readily other methods, means it can provide powerful discrimination prognostic information. The rapid format, error, demonstrates is new high-quality laboratory test an underlying telomeropathy.