Lymphocyte mosaicism in Fanconi anemia: diagnosis and clinical correlation

Background and aim Increased chromosome breakage is the diagnostic feature of Fanconi anemia (FA) owing to genomic instability. Patients with hematopoietic somatic mosaicism are often difficult to identify clinically and diagnostically, although they may comprise up to 25% of patients with FA. The study aimed to clarify the variability of chromosomal breakage test in diagnosis of FA and lymphocyte mosaicism in addition to studying the relation between chromosomal breakage test results and clinical data of the patients. Patients and methods The study included 25 patients with clinical suspicion of FA. Moreover, 225 age-matched and sex-matched healthy volunteers were included as a control group. Chromosomal breakage test at 300-nM mitomycin C (MMC) concentration was done. Results According to the results of chromosomal breakage test at 300-nM MMC concentration, patients were divided into Fanconi and non-Fanconi groups. The mean chromosomal breakage per cell was 4.67 ± 1.58, per aberrant cell was 5.6 ± 1.1, and the mean chromosomal fragility index was 466.7 ± 157 in the Fanconi group, which was significantly different from non-Fanconi group. Patients with FA were further divided into classic Fanconi anemia (CFA) with more than or equal to 10 breaks/cell and Fanconi with mosaicism (FA-Mo) with two cell populations at 300-nM MMC, one like typical FA cells showing more than or equal to 10 breaks/cell, and one like healthy controls, which was largely represented by the categories 0, 1, and 2 breaks/cell. There were significant differences between CFA and FA-Mo regarding results of chromosomal breakage test at 300 nM MMC per cell, per aberrant cell, and the chromosomal fragility index. Insignificant differences were observed between CFA and FA-Mo regarding clinical or hemogram data. Conclusion The present study provided a detailed laboratory protocol for the accurate assessment of the FA diagnosis and enabled a quantitative estimate of the degree of mosaicism in the lymphocyte compartment of the patient.