Fanconi Anemia: Cytogenetic and clinical studies on a group of Fanconi anemia patients in Egypt

Fanconi anemia (FA) is a rare autosomal recessive disease characterized by congenital abnormalities, progressive bone marrow failure and cancer development. This study aimed to use cytogenetic techniques in the evaluation of Fanconi anemia patients and carriers and also to detect the common congenital abnormalities affecting these patients. The study included 48 patients clinically suspected to have FA, 20 parents of proven FA patients and 10 normal individuals as a control group. The studied groups were subjected to clinical evaluation and chromosomal studies, by using the conventional method (G-banding technique) and induction of chromosomal breakage by diepoxy butane(DEB) and mitomycin C (MMC). By using DEB our patients were classified into FA patients (34 cases) and non FA (14 cases). The main clinical findings in FA patients were pancytopenia (90%), limb anomalies (55%) and microcephaly (52%). Consanguineous marriage was found in 97% of FA cases. By DEB technique all FA cases showed the characteristic chromosomal breakage (chromatid exchange figures) in many of their cells. Induction of breakage by DEB gave a wide range of break/cell (br/cell) (1.2-12.1), with mean br/cell 4.3; 60% of the cases had 100% aberrant cells; in the other 40% the aberrant cells ranged from 60 to 91%. 70% of the cases had cells with more than 10 br/cell and some cases showed innumerable breaks in a few cells. On the other hand, the non FA group did not show such aberrations in any of their cells. Adding MMC at the beginning of culture, confirmed the benefit of using this chemical for diagnosing FA patients. All the FA patients exhibited the characteristic breaks in many of their cells by using MMC. 90% of the parents revealed an increase of chromosomal breakage by using DEB but not MMC. Although the results of the parents were statistically significant there was overlap between the parents and the controls. The spontaneous chromosomal breaks results revealed that not all the bands are randomly involved since 32% of the bands were correlated to fragile sites and 65% of the bands were correlated to oncogenes and/or cancer break points. © Hellenic Society of Haematology.