Analysis of Clinical Manifestations in the Spectrum of Patients with Telomeropathies

• Grant number: 23/08753-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2023
• End date: August 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Rodrigo do Tocantins Calado de Saloma Rodrigues
• Grantee: Gustavo Araujo Gonçalves
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Telomeres are structures present at the end of chromosomes made up of repetitive sequences of DNA and associated proteins, whose main function is to maintain the integrity of the genome. With each cell division, telomeres progressively shorten until they reach a critical limit, so that the cell undergoes apoptosis or enters senescence. Certain cell types that have a high replicative demand have the ability to restore and maintain telomere length through the telomerase enzyme complex, which adds DNA sequences back to the end of telomeres. In telomeropathies, pathogenic germline variants in genes involved in telomere maintenance lead to poor cell regeneration and extremely short telomeres, resulting in disorders that affect mainly the bone marrow, but also skin, lungs and liver, in addition to an increased predisposition to development of some neoplasms.Since the clinical manifestations of telomeropathies are extensive and polymorphic, there is no clear evidence of the distribution of phenotypes, their proportions, associations and frequencies. Thus, the present study proposal seeks to establish a relationship between telomere length, germinal variant and clinical manifestations of patients with telomeropathies. The results of this work will be useful to deepen the knowledge of these rare diseases and better understand their clinical spectrum.