Genetic aspects of telomere biology disorders

The presence of germline pathogenic variants (GPVs) in genes involved in telomere length regulation or protection has been demonstrated to be a causative factor for telomere biology disorders (TBDs). TBDs are a group of rare diseases characterized by premature ageing, which exhibit remarkable clinical heterogeneity, with manifestations ranging from pulmonary fibrosis and liver disease in adulthood to bone marrow failure and mucocutaneous anomalies in infancy. To date, pathogenic variants in over 20 telomere-related genes (TRGs) have been implicated, each affecting telomere length or integrity through diverse molecular pathways. This review summarizes the genetic and clinical complexity of TBDs, highlighting challenges in diagnosis and genetic counselling.