The clinical and biological overlap between Nijmegen Breakage Syndrome and Fanconi anemia

• Published in: Clinical immunology (Orlando, Fla.) Vol. 113; no. 2; pp. 214 - 219
• Main Authors: Gennery, A.R., Slatter, M.A., Bhattacharya, A., Barge, D., Haigh, S., O'Driscoll, M., Coleman, R., Abinun, M., Flood, T.J., Cant, A.J., Jeggo, P.A.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.11.2004; Elsevier
• Subjects: Abnormalities, Multiple - genetics; Abnormalities, Multiple - immunology; Abnormalities, Multiple - pathology; Biological and medical sciences; Blotting, Western; Cell Cycle Proteins - genetics; Chromosomal instability; Chromosome Breakage - genetics; Chromosome Breakage - immunology; Diagnosis, Differential; Fanconi anemia; Fanconi Anemia - genetics; Fanconi Anemia - immunology; Fanconi Anemia - physiopathology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunodeficiency; Immunoglobulins - blood; Immunopathology; Infant, Newborn; Lymphocytes - immunology; Male; Medical sciences; Mutation; Nijmegen Breakage Syndrome; Nuclear Proteins - genetics; Phenotype; Radiosensitivity; Receptors, Antigen, T-Cell - genetics; Radiosensitivity; Chromosomal instability; Fanconi anemia; Nijmegen Breakage Syndrome; Immunodeficiency; Chromosome fragility; Immunopathology; Nervous system diseases; Nijmegen breakage syndrome; Hemopathy; Malignant tumor; Immune deficiency; Genetic disease; Immunology
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2004.03.024

Fanconi anemia (FA), an autosomal recessive chromosomal instability syndrome, is characterized clinically by developmental abnormalities, growth retardation, progressive bone marrow failure, pancytopenia, and pronounced cancer predisposition. Nijmegen Breakage Syndrome (NBS) is a related disorder that shares overlapping clinical features, principally, developmental delay, microcephaly, and cancer predisposition. The diagnosis has relied on chromosomal instability following exposure to DNA cross-linking agents in FA and to ionizing radiation (IR) in NBS. We describe two patients who clinically had FA, but showed sensitivity to both DNA cross-linking agents and ionizing radiation, and who were found to have a rare mutation in the NBS gene. The importance of genetic diagnosis with respect to treatment and prognosis is discussed.