Cytogenetic and clinical analysis on a rare chromosomal breakage disorder- Fanconi Anemia

Kharbuli, Iakmenlang S (2023) Cytogenetic and clinical analysis on a rare chromosomal breakage disorder- Fanconi Anemia. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS dissertation of Iakmenlang S Kharbuli (18MS138)) Thesis_18MS138.pdf - Submitted Version Restricted to Repository staff only Download (1MB)

Abstract

Fanconi anemia is a heterogeneous autosomal recessive disorder which is associated with bone marrow failure, developmental abnormalities and an increased risk for cancer. To date, twenty-three genes have been identified in the causation, the most prevalent being FANCA, FANCC, FANCG and FANCD2, which produce proteins that work together in a genome maintenance and repair pathway called the FA pathway. The FA pathway which is an essential tumor-suppressive pathway protects the human genome from DNA damage, particularly inter-strand crosslinks. Mutations in the FA genes can result in them being dysfunctional to DNA repair. Through varied mechanisms, these mutations can disrupt the entire FA pathway, preventing the repair of DNA aberrations like inter-strand cross-links. Unrepaired inter-strand cross-links (ICLs) are a major source of genome instability and are responsible for the many different FA patient phenotypes. This monogenic disorder is manifested by hypersensitivity to DNA cross-linking agents and a high degree of chromosomal aberrations. Mutations in all 23 known FA genes are first tested by a cytogenetic test known as the chromosomal breakage test, which is the gold standard for identifying FA. In addition to studying the induced chromosome breakages in blood samples of affected individuals, the retrospective data of FA-affected patients attending CGH OPD was studied over a 12-year period from the medical notes. The clinical findings of 32 distinct FA cases, ages ranging from infancy to 17 years are presented here. The most common clinical characteristics of FA patients along with the cytogenetic analysis are discussed in this study.

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