Telomeropathies: Etiology, diagnosis, treatment and follow‐up. Ethical and legal considerations

Abstract

Telomeropathies involve a wide variety of infrequent genetic diseases caused by mutations in the telomerase maintenance mechanism or the DNA damage response (DDR) system. They are considered a family of rare diseases that often share causes, molecular mechanisms and symptoms. Generally, these diseases are not diagnosed until the symptoms are advanced, diminishing the survival time of patients. Although several related syndromes may still be unrecognized this work describes those that are known, highlighting that because they are rare diseases, physicians should be trained in their early diagnosis. The etiology and diagnosis are discussed for each telomeropathy and the treatments when available, along with a new classification of this group of diseases. Ethical and legal issues related to this group of diseases are also considered.

Telomere and Centromere Staining Followed by M-FISH Improves Diagnosis of Chromosomal Instability and Its Clinical Utility

“…Although long telomeres may be associated with higher telomerase activity in certain cancers [20,36,37], telomere shortening represents the main mechanism of senescence and tumor initiation and progression. In addition, growing interest in the implication of telomere dysfunction in genetic disorders has been recently addressed [38,39]. The development of a faster and more efficient diagnostic approach for the detection of telomere dysfunction in cytogenetic clinical practice is necessary to not only better target cancer cells and genetic disorders but also to monitor populations exposed to genotoxic agents.…”

New drugs are not enough‑drug repositioning in oncology: An update

“…In each cell division, every chromosome is duplicated, but DNA polymerases cannot copy all bases in the 3' end after primer removal, which results in the loss of a certain number of telomeric sequences in every cycle. Then, telomeres shorten progressively; when telomere length is critical, the cell enters into senescence and apoptosis (542). In the case of germinal or stem cells, they do not have an incomplete replication process; to solve this issue, the vast majority of organisms use a specific mechanism to maintain telomere length, executed by a specialized holoenzyme called telomerase (543).…”

Selection Criteria for Lung Transplantation: Controversies and New Developments

“…These patients may then be analyzed for telomere mutations. 147,148 As pretransplant peripheral blood count is not a reliable indicator for bone marrow function, pretransplant challenge protocols with immunosuppressive drugs could be used to test the robustness of bone marrow reserves and identify patients who can tolerate the hematological stress of transplant-related myelosuppressive medications; alternatively, this group could be screened for subclinical disease using bone marrow biopsy. 139,142 Also, since this group of patients is at a higher risk for hematological complications, one might consider removing the antiproliferative agent (mycophenolate mofetil or azathioprine) from the post-lung transplantation drug regimen.…”