ORPHA: 84; DO: 0111081;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q32.1 | Fanconi anemia, complementation group T | 616435 | Autosomal recessive | 3 | UBE2T | 610538 |
A number sign (#) is used with this entry because of evidence that Fanconi anemia of complementation group T (FANCT) is caused by compound heterozygous mutation in the UBE2T gene (610538) on chromosome 1q32.
Fanconi anemia is characterized by genomic instability, increased susceptibility to cancer development, and bone marrow failure associated with various developmental abnormalities, such as radial ray anomalies or short stature (summary by Hira et al., 2015).
For a discussion of genetic heterogeneity of Fanconi anemia, see FANCA (227650).
Hira et al. (2015) reported 2 unrelated Japanese patients, a girl (PNGS-252) and a boy (PNGS-255), with Fanconi anemia. Both patients presented at birth with thumb abnormalities: the girl had a hypoplastic thumb and the boy had bilateral thumb polydactyly. The girl also had short stature and abnormalities of external genitalia, whereas the boy had facial palsy and dysplasia of the middle ear bone. Both were found to have thrombocytopenia and anemia as well as increased rate of chromosomal breakage. The girl developed pancytopenia, and the boy was diagnosed with refractory anemia evolving to acute myeloid leukemia associated with a somatic 3q abnormality. Both received bone marrow transplantation, which was successful in the girl; however, the boy died at age 8 years.
The transmission pattern of FANCT in the families reported by Hira et al. (2015) was consistent with autosomal recessive inheritance.
In 2 unrelated Japanese patients with FANCT, Hira et al. (2015) identified mutations in the UBE2T gene. Both patients carried a missense mutation (Q2E; 610538.0001 on 1 allele; patient PNGS-255 carried a splice site mutation 610538.0002) on the other allele, and patient PNGS-252 carried a 23-kb deletion encompassing almost the entire UBE2T gene and part of the LGR6 gene (606653) on the other allele. The exact breakpoints of the deletion could not be determined. The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Cells derived from patient PNGS-252 showed increased levels of mitomycin C-induced chromosome breakage, which was rescued by expression of wildtype UBE2T. In vitro functional expression assays and studies on cells derived from patient PNGS-252 showed that the Q2E mutation abolished FANCD2 (613984) monoubiquitination and interaction with FANCL (608111).
Hira, A., Yoshida, K., Sato, K., Okuno, Y., Shiraishi, Y., Chiba, K., Tanaka, H., Miyano, S., Shimamoto, A., Tahara, H., Ito, E., Kojima, S., Kurumizaka, H., Ogawa, S., Takata, M., Yabe, H., Yabe, M. Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi anemia. Am. J. Hum. Genet. 96: 1001-1007, 2015. [PubMed: 26046368] [Full Text: https://doi.org/10.1016/j.ajhg.2015.04.022]