Age-specific telomere length percentiles in the Argentine population: a diagnostic tool for telomere biology disorders

Introduction. Telomere length (TL) is a biomarker of cellular aging. Its excessive shortening is associated with telomere biology disorders (TBD), which can manifest from childhood with bone marrow failure and a predisposition to cancer. The clinical interpretation of TL requires age-adjusted reference curves specific to each population. In Argentina, there is no curve of its own. The objective of the study was to construct an age-adjusted telomere length reference curve representative of the Argentine population. Methods. Using the Monochrome Multiplex Quantitative PCR (MMQPCR) technique, TL was estimated in 159 samples from healthy individuals (0-50 years old). The percentile curve was adjusted using a generalized linear model with a gamma distribution. Validation was performed using 19 controls (normal and pathological) that had previously been evaluated by MMQPCR or Southern blot in international laboratories. Results. The curve allowed us to estimate age-adjusted TL percentiles (P1-P95). All samples with a clinical or molecular diagnosis of TBD were below P10, and cases with severe phenotypes were below P1. Normal controls were above P10. The technique demonstrated good reproducibility and adequate model adjustment. Conclusions. The first age-adjusted TL reference curve was generated in the Argentine population. It is a valuable tool for local laboratories that use the same methodology, guiding the diagnosis of TBD. Its integration with next-generation sequencing techniques increases diagnostic sensitivity and allows for a more accurate approach to these syndromes.