ORPHA: 84; DO: 0111086;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 9p13.3 | Fanconi anemia, complementation group G | 614082 | Autosomal recessive | 3 | XRCC9 | 602956 |
A number sign (#) is used with this entry because Fanconi anemia of complementation group G (FANCG) is caused by homozygous or compound heterozygous mutation in the FANCG gene on chromosome 9p13.
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.
In 20 patients with FANCG, 4 of whom had been reported by de Winter et al. (1998), Demuth et al. (2000) found that the phenotypic heterogeneity characteristic of FA was clearly demonstrated, even within sib pairs showing discordance for several symptoms. The average age of hematologic onset in this group of patients was 6.1 years, not significantly different from that found in other FA complementation groups.
In patients with Fanconi anemia of complementation group G, de Winter et al. (1998) identified mutations in the XRCC9 (FANCG) gene (602956.0001-602956.0002).
Demuth et al. (2000) identified 18 different mutations in the FANCG gene in a panel of 20 FANCG patients, 4 of whom had been reported by de Winter et al. (1998). By using SSCP analysis and sequencing, they identified 39 of 40 mutant alleles. Most of the mutations (94%) were expected to result in protein truncation, and only 1 missense mutation was detected. The 18 mutations showed no obvious clustering within the gene.
Auerbach et al. (2003) studied the distribution of FANCG mutations in the populations covered by the International Fanconi Anemia Registry. They found the most common FANCG mutations were IVS8-2A-G (602956.0005), seen in 7 Portuguese-Brazilian probands; IVS11+1G-C (602956.0006), seen in 7 French-Acadian probands; 1794-1803del10 (602956.0007), seen in 7 European probands; and IVS3+1G-C (602956.0003), seen in 5 Korean or Japanese probands. Auerbach et al. (2003) suggested that the Portuguese-Brazilian, French-Acadian, and Korean/Japanese mutations were present in a founding member of each of these populations.
Auerbach, A. D., Greenbaum, J., Pujara, K., Batish, S. D., Bitencourt, M. A., Kokemohr, I., Schneider, H., Lobitz, S., Pasquini, R., Giampietro, P. F., Hanenberg, H., Levran, O. Spectrum of sequence variation in the FANCG gene: an International Fanconi Anemia Registry (IFAR) study. Hum. Mutat. 21: 158-168, 2003. Note: Erratum: Hum. Mutat. 22: 255 only, 2003. [PubMed: 12552564] [Full Text: https://doi.org/10.1002/humu.10166]
Deakyne, J. S., Mazin, A. V. Fanconi anemia: at the crossroads of DNA repair. Biochemistry 76: 36-48, 2011. [PubMed: 21568838] [Full Text: https://doi.org/10.1134/s0006297911010068]
Demuth, I., Wlodarski, M., Tipping, A. J., Morgan, N. V., de Winter, J. P., Thiel, M., Grasl, S., Schindler, D., D'Andrea, A. D., Altay, C., Kayserili, H., Zatterdale, A., Kunze, J., Ebell, W., Mathew, C. G., Joenje, H., Sperling, K., Digweed, M. Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9. Europ. J. Hum. Genet. 8: 861-868, 2000. [PubMed: 11093276] [Full Text: https://doi.org/10.1038/sj.ejhg.5200552]
de Winter, J. P., Waisfisz, Q., Rooimans, M. A., van Berkel, C. G. M., Bosnoyan-Collins, L., Alon, N., Carreau, M., Bender, O., Demuth, I., Schindler, D., Pronk, J. C., Arwert, F., Hoehn, H., Digweed, M., Buchwald, M., Joenje, H. The Fanconi anaemia group G gene FANCG is identical with XRCC9. Nature Genet. 20: 281-283, 1998. [PubMed: 9806548] [Full Text: https://doi.org/10.1038/3093]