2. Academic Validation
  3. Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi anemia

Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi anemia

  • Am J Hum Genet. 2015 Jun 4;96(6):1001-7. doi: 10.1016/j.ajhg.2015.04.022.
Asuka Hira 1,  Kenichi Yoshida 2,  Koichi Sato 3,  Yusuke Okuno 4,  Yuichi Shiraishi 5,  Kenichi Chiba 5,  Hiroko Tanaka 6,  Satoru Miyano 7,  Akira Shimamoto 8,  Hidetoshi Tahara 8,  Etsuro Ito 9,  Seiji Kojima 4,  Hitoshi Kurumizaka 3,  Seishi Ogawa 2,  Minoru Takata 10,  Hiromasa Yabe 11,  Miharu Yabe 11
Affiliations

Affiliations

  • 1 Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan.
  • 2 Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
  • 3 Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan.
  • 4 Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
  • 5 Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
  • 6 Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
  • 7 Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
  • 8 Department of Cellular and Molecular Biology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan.
  • 9 Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
  • 10 Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan. Electronic address: [email protected].
  • 11 Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara 259-1193, Japan.
PMID: 26046368 DOI: 10.1016/j.ajhg.2015.04.022
Abstract

Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, increased Cancer susceptibility, progressive bone marrow failure (BMF), and various developmental abnormalities resulting from the defective FA pathway. FA is caused by mutations in genes that mediate repair processes of interstrand crosslinks and/or DNA adducts generated by endogenous aldehydes. The UBE2T E2 ubiquitin conjugating Enzyme acts in FANCD2/FANCI monoubiquitination, a critical event in the pathway. Here we identified two unrelated FA-affected individuals, each harboring biallelic mutations in UBE2T. They both produced a defective UBE2T protein with the same missense alteration (p.Gln2Glu) that abolished FANCD2 monoubiquitination and interaction with FANCL. We suggest this FA complementation group be named FA-T.

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