THE FANCONI-ANEMIA GROUP-G GENE FANCG IS IDENTICAL WITH XRCC9

Fanconi anemia (FA) is an autosomal recessive disease with diverse cli nical symptoms including developmental anomalies, bone marrow failure and early occurrence of malignancies'. In addition to spontaneous chro mosome instability, FA cells exhibit cell cycle disturbances and hyper sensitivity to crosslinking agents(1). Eight complementation groups (A -H) have been distinguished(2), each group possibly representing a dis tinct FA gene(3). The genes mutated in patients of complementation gro ups A (FANCA; refs 4,5) and C (FANCC; ref. 6) have been identified, an d FANCD has been mapped to chromosome band 3p22-26 (ref. 7). An additi onal FA gene has recently been mapped to chromosome 9p (ref. 8). Here we report the identification of the gene mutated in group G, FANCG, on the basis of complementation of an FA-G cell line and the presence of pathogenic mutations in four FA-C patients. We identified the gene as human XRCC9, a gene which has been shown to complement the MMC-sensit ive Chinese hamster mutant UV40, and is suspected to be involved in DN A post-replication repair or cell cycle checkpoint control(9,10). The gene is localized to chromosome band 9p13 (ref. 9), corresponding with a known localization of an FA gene.