Telomere Biology Disorders

Telomere biology disorders, also called telomeropathies, are a group of rare genetic conditions characterized by telomeres that are longer or shorter than usual. Even though telomere biology disorders are genetic, symptoms can appear in both kids and adults — sometimes in people over 60 years old.

Telomeres are long segments at the ends of chromosomes that protect DNA from coming apart, similar to the plastic piece at the end of a shoelace. In healthy people, telomeres shorten naturally with age. But in people with telomere biology disorders, their telomeres become shorter than usual — or, in certain disorders, longer than usual. People with these disorders are susceptible to a variety of age-related conditions, including:

  • Bone marrow failure.
  • Cancer.
  • Liver fibrosis.
  • Osteoporosis.
  • Pulmonary fibrosis.

Many but not all people with telomere biology disorders show signs of premature aging, such as premature graying of hair or brittle nails.

Care at Mayo Clinic

Telomere biology disorders are complex conditions that require a coordinated approach to offer the best care. To meet the specific needs of people with these conditions, Mayo Clinic established the Telomere Biology Disorders Clinic in 2017. This clinic brings together experts from many areas, including:

  • Gastroenterologists.
  • Genetic counselors.
  • Hematologists.
  • Liver specialists.
  • Molecular biologists.
  • Oncologists.
  • Pharmacists.
  • Pulmonologists.
  • Transplant physicians.

This team approach ensures that patients can benefit from the knowledge of multiple experts at the same time, making care faster and more unified.

The Telomere Biology Disorders Clinic uses an algorithmic clinical approach to diagnose patients and manage their care. This approach includes measuring telomere length and testing for genetic mutations — including both germline mutations, which are passed down from family members, and somatic mutations, which happen randomly and are not passed down.

Doctors and researchers at Mayo Clinic have extensive experience evaluating and treating people with telomere biology disorders. To date, the Telomere Biology Disorders Clinic has seen and diagnosed more than 100 people with telomere biology disorders. In 2024, Team Telomere recognized Mayo Clinic as a tier 1 Center of Excellence. Team Telomere is the main advocacy group in the United States for people with telomere biology disorders. Learn more about Team Telomere on the organization's website.

Research to improve care

No effective treatments currently exist to cure telomere biology disorders. So far, patient care is limited to preventive strategies, supportive care and organ transplantation. But recent advancements in gene editing and gene therapy offer hope for the future.

In 2021, with support from the Center for Individualized Medicine and the Division of Hematology, Mayo Clinic established the Telomere Translational Program to advance research on these disorders and support the Telomere Biology Disorders Clinic. This program aims to achieve new understanding of the entire spectrum of telomere biology disorders. Program researchers are involved in multiple in-house and multicenter collaborative research studies and projects to improve diagnosis and care for patients with telomere biology disorders.

The main areas of telomere biology disorder research taking place at Mayo Clinic include:

  • Functional testing of variants of uncertain significance. Genetic testing often uncovers suspicious variants in genes related to telomere biology disorders but doesn't give enough information to ascertain pathogenicity. These variants of uncertain significance complicate diagnosis and require additional testing to ascertain pathogenicity. The Telomere Translational Program has established functional testing workflows to test most of these variants.

  • Clinical significance of somatic mosaic states in telomere biology disorders. Program researchers and others have shown that the bone marrow of patients with telomere biology disorders favors the emergence of somatic mosaic states. These states are hypothesized to be a form of rescue hematopoiesis, with unclear long-term outcomes and dynamics. Parallel to the Telomere Biology Disorders Specialty Clinic, Mayo Clinic established a clonal hematopoiesis clinic that has implemented a testing workflow to find and study somatic alterations in hematopoietic stem and progenitor cells.

    Leveraging this expertise, researchers are developing initiatives to define the clinical significance and evolution of clonal hematopoiesis in telomere biology disorders and to implement this knowledge in routine clinical care. This information also could help identify therapeutic vulnerabilities that might halt the development of blood cancers in these patients.

  • Multi-omic analysis of telomere biology disorders. Only 60% of adult patients seen at Mayo Clinic for telomere biology disorders present a pathogenic variant that is known to lead to this condition. Telomere Translational Program researchers perform exome and genome sequencing of selected patients to identify previously undiscovered causes of telomere biology disorder. They complement this analysis with RNA-seq, single-cell DNA sequencing and epigenomic testing on a research basis.

  • Chromosome-specific telomere length dynamics in telomere biology disorders. Current tests for telomere biology disorders measure the average length of all telomeres but do not account for individual telomere length variability between chromosomes. This creates diagnostic uncertainty when the measured value is on the border between healthy and atypical — for example, between the first and 10th centile. Therefore, more sensitive and specific detection methods are needed.

    Program researchers have developed bioinformatic methods that use long-read sequencing data to measure individual telomere lengths at the chromosome-arm level. This new approach may help identify patients with telomere biology disorders more accurately and may facilitate future research studies in the etiopathogenesis of the disorders.

Review published telomere biology disorder research by Mayo Clinic authors on PubMed.