Mitotic instability influence on clinical heterogeneity in patients with ring chromosomes

• Grant number: 24/02492-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2024
• End date: June 30, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Társis Antônio Paiva Vieira
• Grantee: Érico de Carvalho Leitão Pimentel
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Ring chromosomes consist of structural abnormalities characterized by an atypical circular configuration, which can result in unstable behavior during cell division, termed dynamic mosaicism. The phenotype of individuals carrying ring chromosomes is influenced primarily by the affected chromosome and the deleted gene regions during the ring formation process. However, the relation between secondary abnormalities derived from mitotic instability and the clinical presentation of these patients is not fully understood. This study aims to investigate the contribution of mitotic instability of ring chromosomes to patient phenotype. Clinical characterization of patients with acrocentric ring chromosomes will be conducted, along with investigation of secondary alterations, and clinical comparison with patients without the ring but with similar deletions. The study will include ten patients with acrocentric ring chromosomes. Clinical characterization will involve utilizing clinical data from medical records, which will be coded according to the Human Phenotype Ontology (HPO). Investigation of secondary abnormalities (aneuploid cells) will be performed using the fluorescence in situ hybridization method on cultured peripheral blood lymphocytes and oral mucosa cells. Phenotypic comparison will be done utilizing data from the literature, obtained through systematic review.