Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder that causes genomic instability. Characteristic clinical features include developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer. The cellular hallmark of ... Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder that causes genomic instability. Characteristic clinical features include developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer. The cellular hallmark of FA is hypersensitivity to DNA crosslinking agents and high frequency of chromosomal aberrations pointing to a defect in DNA repair (summary by Deakyne and Mazin, 2011). For additional general information and a discussion of genetic heterogeneity of Fanconi anemia, see 227650.
Levitus et al. (2004) provided a tabulation of 11 genetically distinct FA subtypes. They reported 8 unrelated FA patients who were excluded from the known subtypes on the basis of phenotypic correction (complementation) or genetic data. Four of ... Levitus et al. (2004) provided a tabulation of 11 genetically distinct FA subtypes. They reported 8 unrelated FA patients who were excluded from the known subtypes on the basis of phenotypic correction (complementation) or genetic data. Four of these cell lines failed to complement each other in somatic cell hybrids and therefore represented a new group, termed complementation group I (FANCI). The remaining cell lines complemented group FANCI but did not complement each other, thus representing a second new group, FANCJ (609054). Both the FANCI and FANCJ cell lines were capable of forming an FA multiprotein core complex. This complex is required for activation of the FANCD2 protein (227646) by monoubiquitination, a key downstream event in the FA pathway. In FANCI cells, FANCD2 was not monoubiquitinated, indicating a defect upstream in the FA pathway, whereas in FANCJ cells, FANCD2 was monoubiquitinated, indicating a downstream defect. The results suggested that the FA pathway of genome stabilization may be controlled by at least 11 different genes, including FANCI and FANCJ.
Dorsman et al. (2007) identified several mutations in the FANCI gene (e.g., 611360.0001 to 611360.0004) in 8 patients with FA complementation group I. Western blot analysis confirmed that functionally active FANCI protein was absent in patients with FA ... Dorsman et al. (2007) identified several mutations in the FANCI gene (e.g., 611360.0001 to 611360.0004) in 8 patients with FA complementation group I. Western blot analysis confirmed that functionally active FANCI protein was absent in patients with FA complementation group I. Sims et al. (2007) and Smogorzewska et al. (2007) also reported mutations in the FANCI gene in patients with FA complementation group I.