Caracterización genética de la anemia de Fanconi en población colombiana, relación con el fenotipo clínico y citogenético

Student thesis: Doctoral thesis

Abstract

Fanconi Anemia (FA) is caused by defects in genes that participate in DNA repair pathways and in the regulation of cell cycle processes. Thus, different aspects of the development and survival of an individual are affected. Fanconi anemia is highly heterogeneous ranging from severe to mild phenotypes, which makes diagnosis difficult. Characteristically, those affected present congenital malformations, bone marrow aplasia, predisposition to cancer, and chromosome instability. Due to the unknown etiology in Colombia, it was proposed to characterize affected FA individuals, identified from patients with a diagnosis or from individuals with FA clinical suspicion. 157 individuals with diagnosis or clinical suspicion were recruited, 19 with VACTERL association, 15 siblings of FA cases, and 34 healthy individuals. Clinical manifestations were recorded and hypersensitivity to diepoxybutane cytogenetic tests was performed. Molecular characterization of hypersensitive FA cases was carried out by MLPA for FANCA, NGS for FANC gene panel, and Sanger sequencing. 43 cases were classified as FA by cytogenetic test, where the genotype was established for 24. 22(91.6%) with alterations in FANCA, 1(4.2%) in FANCB and 1 (4.2%) in FANCD2. Identified variants were large deletions and INDEL mutations and base substitution mutations. 10(47.6%) were new variants. The most prevalent clinical signs included hematological, skeletal, skin-related, face and height alterations. This study reports for the first time in Colombia on the genetic characteristics of the disease, confirming a high prevalence of FANCA (91.6%) alterations, greater than the average reported for other populations. Most variants were unique, although an identified FANCA variant in several cases with common regional origin was noteworthy.
Date of Award9 Sept 2023
Original languageSpanish
Awarding Institution
  • Universitat Autònoma de Barcelona (UAB)
  • Pontificia Universidad Javeriana
SupervisorJavier Benítez (Director) & Jordi Surralles Calonge (Director)

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