Cytogenetic diagnosis of FA in a cohort of patients with clinical characteristics of suspected Fanconi anemia
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Abstract
Background: Fanconi Anemia (FA) is an inherited disease that affects DNA repair. Clinically, it is heterogeneous; congenital malformations, early bone marrow aplasia, and a predisposition to cancer are present. The genetic defect causes hypersensitivity to genotoxic agents and chromosomal instability; this feature is considered the best diagnostic marker; however, reaching it can be challenging. Objective: To characterize patients with FA using cytogenetic tests in individuals with clinical features suggestive of the disease. Methods: 157 individuals with clinical suspicion of FA, 19 with VACTERL association, 15 siblings, and 34 healthy individuals were analyzed. Recording of clinical data and cytogenetic tests with Diepoxybutane (DEB) were performed. Results: 43 people affected by AF were identified. The ratio of indices in DEB-treated cells of the AF group vs. No-AF was significantly increased: 6.7-fold the proportion of aberrant cells, 48-fold the number of breaks per cell, and 6.3-fold the number of breaks per aberrant cell. In FA, the mean sampling age was 9.2 years, the sex ratio M:F was 1.5:1, and consanguinity was present in 11 cases. The hematologic, skeletal, integumentary, and urinary systems were significantly altered. Conclusions: FA was identified in 26% of the suspected group and in 13% of siblings without prior suspicion. The hematological disease was the most recurrent symptom present in 93% of cases and was mainly the first suspicion of FA and the reason for genetic study.
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