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.
Meetei et al. (2005) screened cells derived from individuals with Fanconi anemia for FAAP250 mutations by immunoblotting. They detected FAAP250 in cells from individuals with all known complementation groups, implying that if FAAP250 is mutant in individuals with ... Meetei et al. (2005) screened cells derived from individuals with Fanconi anemia for FAAP250 mutations by immunoblotting. They detected FAAP250 in cells from individuals with all known complementation groups, implying that if FAAP250 is mutant in individuals with Fanconi anemia, this would constitute a new complementation group. FAAP250 was undetectable in a cell line from 1 individual who was excluded from many known complementation groups by linkage analysis, cell fusion, and cDNA transfection. Sequencing of this individual's cDNA identified a nonsense mutation (609644.0001) in exon 13 and absence of sequence encoded by exon 15 caused by a deletion (609644.0002). These mutations were predicted to lead to truncated products of 80 kD and 160 kD, respectively, but neither product was detectable, suggesting that they may be unstable. The nonsense mutation was inherited from the mother; 2 sibs had the deletion mutation, which was not identified in the father. Consequently, the father was considered to be a gonadal mosaic for the mutation.