Alternative titles; symbols
ORPHA: 84; DO: 0111084;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 6p21.31 | Fanconi anemia, complementation group E | 600901 | Autosomal recessive | 3 | FANCE | 613976 |
A number sign (#) is used with this entry because Fanconi anemia complementation group E is caused by homozygous mutation in the FANCE gene (613976) on chromosome 6p21.
Fanconi anemia (FA) is characterized by bone marrow failure, developmental abnormalities, cancer predisposition, and cellular hypersensitivity to DNA cross-linking agents such as mitomycin C (summary by de Winter et al., 2000).
For additional general information and a discussion of genetic heterogeneity of Fanconi anemia, see 227650.
Joenje et al. (1995) presented evidence for a fifth subtype of Fanconi anemia, designated group E. Buchwald (1995) stated that 6 of 31 patients (12.7%) could be classified as group E. The FACE group is defined as being different from groups A (607139), B (300514), C (227645), and D (227646), and may itself be heterogeneous.
Wegner et al. (1996) also described the fifth Fanconi anemia complementation group. Their first patient, a Turkish boy, presented with psychomotor retardation, growth retardation, retarded bone age, brachycephaly, hypotelorism, epicanthus, syndactyly, brachydactyly, renal dystopia, and cryptorchidism. In addition, an asymmetric skeletal anomaly was seen with a double distal phalanx of the left thumb and hypoplasia of the right thumb. Typical hematologic features of the disorder developed at the age of 2.5 years, about 1 year after initial diagnosis. Cytogenetic studies confirmed the clinical diagnosis and revealed a spontaneous chromosomal instability and hypersensitivity to the cross-linking agents diepoxybutane and Trenimon. The findings in the patient were compared with data reported for other patients with Fanconi anemia.
Following the identification of the first FACE patient (Joenje, 1996), additional patients were identified whose cell lines complemented groups A-D. To assess their possible assignment to group E, Joenje et al. (1997) extended the complementation analysis by introducing suitable selection markers into the original FACE cell line and 3 cell lines classified as non-ABCD. The results indicated that each of these 3 cell lines represented a new complementation group, implying existence of at least 8 complementation groups in Fanconi anemia, including the 3 new groups FACF, FACG, and FACH.
Waisfisz et al. (1999) reported the use of homozygosity mapping and genetic linkage analysis to map the FANCE locus to 6p22-p21 in an interval of 18.2 cM flanked by markers D6S422 and D6S1610. Three small families were assigned to group FA-E by cell fusion and complementation analysis. Studies showed that data from even a small number of families can be successfully used to map a gene for a genetically heterogeneous disorder. At that time, 4 of the 8 known complementation groups had been mapped to specific sites and the specific gene had been isolated in the case of 3.
In 3 patients with Fanconi anemia, 2 from Turkey and 1 from Bangladesh, de Winter et al. (2000) identified homozygous mutations in the FANCE gene (613976.0001-613976.0003).
Buchwald, M. Complementation groups: one or more per gene? Nature Genet. 11: 228-230, 1995. [PubMed: 7581439] [Full Text: https://doi.org/10.1038/ng1195-228]
de Winter, J. P., Leveille, F., van Berkel, C. G. M., Rooimans, M. A., van der Weel, L., Steltenpool, J., Demuth, I., Morgan, N. V., Alon, N., Bosnoyan-Collins, L., Lightfoot, J., Leegwater, P. A., Waisfisz, Q., Komatsu, K., Arwert, F., Pronk, J. C., Mathew, C. G., Digweed, M., Buchwald, M., Joenje, H. Isolation of a cDNA representing the Fanconi anemia complementation group E gene. Am. J. Hum. Genet. 67: 1306-1308, 2000. Note: Erratum: Am. J. Hum. Genet. 67: 1365 only, 2000. [PubMed: 11001585] [Full Text: https://doi.org/10.1016/S0002-9297(07)62959-0]
Joenje, H., Lo Ten Foe, J. R., Oostra, A. B., van Berkel, C. G. M., Rooimans, M. A., Schroeder-Kurth, T., Wegner, R.-D., Gille, J. J. P., Buchwald, M., Arwert, F. Classification of Fanconi anemia patients by complementation analysis: evidence for a fifth genetic subtype. Blood 86: 2156-2160, 1995. [PubMed: 7662964]
Joenje, H., Oostra, A. B., Wijker, M., di Summa, F. M., van Berkel, C. G. M., Rooimans, M. A., Ebell, W., van Weel, M., Pronk, J. C., Buchwald, M., Arwert, F. Evidence for at least eight Fanconi anemia genes. Am. J. Hum. Genet. 61: 940-944, 1997. [PubMed: 9382107] [Full Text: https://doi.org/10.1086/514881]
Joenje, H. Fanconi anaemia complementation groups in Germany and The Netherlands. Hum. Genet. 97: 280-282, 1996. [PubMed: 8786063] [Full Text: https://doi.org/10.1007/BF02185753]
Waisfisz, Q., Saar, K., Morgan, N. V., Altay, C., Leegwater, P. A., de Winter, J. P., Komatsu, K., Evans, G. R., Wegner, R.-D., Reis, A., Joenje, H., Arwert, F., Mathew, C. G., Pronk, J. C., Digweed, M. The Fanconi anemia group E gene, FANCE, maps to chromosome 6p. Am. J. Hum. Genet. 64: 1400-1405, 1999. [PubMed: 10205272] [Full Text: https://doi.org/10.1086/302385]
Wegner, R.-D., Henrichs, I., Joenje, H., Schroeder-Kurth, T. Fanconi anemia complementation group E: clinical and cytogenetic data of the first patient. Clin. Genet. 50: 479-482, 1996. [PubMed: 9147877] [Full Text: https://doi.org/10.1111/j.1399-0004.1996.tb02716.x]