Clinical and molecular correlates from a predominantly adult cohort of patients with short telomere lengths

This is the authors' abstract. We don't add key points for this paper.

Telomere biology disorders (TBDs) are accelerated aging syndromes affecting hematopoietic, pulmonary, hepatobiliary, and/or immunological systems among others [ 1 , 2 ]. Adult-onset TBDs are commonly associated with pathogenic variants in TERT and TERC , and manifest with varying degree of organ involvement such as idiopathic interstitial pneumonia (IIP), cryptogenic cirrhosis, unexplained bone marrow failure (BMF) and/or immunodeficiency, and an inherent risk for cancer development such as myeloid leukemias and squamous cell carcinomas among others [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Though fluorescence in-situ hybridization (FlowFISH)-determined age-adjusted lymphocyte TL > 50 %tile have a 100% negative predicted value for variant detection, the TL threshold below which genetic screening should be pursued (especially in older patients) is still not known [ 10 , 11 ]. The optimal TL threshold for variant detection depends on age, with individuals at ages <20 years showing strong correlations with lower TL, while the TL in older variant carriers often overlaps with the lower decile of normal controls [ 10 ]. Genetic screening is suggested for TL ≤ 10th centile in lymphocytes or granulocytes, especially in the presence of suggestive personal or family history of a TBD [ 1 ]. However, the utility of genetic testing for adult patients with TL > 10th centile and integration of clinical phenotype is currently unclear. Additionally, natural outcomes and diagnostic algorithms are less clear in adult (age ≥ 18 years) patients with short telomeres (defined as TL ≤ 10th centile in lymphocytes).