Recent advances in understanding telomere diseases.

Area of Science:

• Genetics and Molecular Biology
• Hematology
• Pulmonology
• Hepatology

Background:

• Germline genetic defects affecting telomere length maintenance cause a spectrum of severe human diseases.
• These telomeropathies are characterized by excessive telomere erosion, impacting cell proliferation, tissue regeneration, and genomic stability.
• Telomere shortening is linked to stem cell fate imbalance, inflammation, and the senescence-associated secretory phenotype.

Purpose of the Study:

• To summarize the clinical manifestations, underlying molecular mechanisms, diagnostic approaches, and current treatment limitations of telomere diseases.
• To highlight the increased risk of malignancies and the potential of novel therapeutic strategies.

Main Methods:

• Review of clinical findings and molecular mechanisms of telomere diseases.
• Discussion of diagnostic tools including telomere length measurement and genetic testing.
• Analysis of current treatment options and emerging therapeutic avenues.

Main Results:

• Telomere diseases manifest with bone marrow failure, pulmonary fibrosis, liver cirrhosis, and increased cancer risk (myeloid neoplasms, head and neck cancer).
• Next-generation sequencing (NGS) has identified at least 16 implicated genes and aids in tracking clonal hematopoiesis and malignant transformation.
• While organ transplantation offers definitive treatment, its availability and impact on comorbidities are limited; androgens show promise in clinical trials for hematopoiesis improvement.

Conclusions:

• Telomere diseases represent a group of rare but severe conditions with significant morbidity and mortality.
• Further research into telomere erosion's impact on organ function and somatic mutation evolution is crucial for developing effective treatments and preventative strategies.
• Early diagnosis and comprehensive management are essential for patients with telomere-related disorders.