title: Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi anemia.
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.
authors.affiliation: Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Hira
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuno
authors.affiliation: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Shiraishi
authors.affiliation: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Chiba
authors.affiliation: Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: 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.
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyano
authors.affiliation: Department of Cellular and Molecular Biology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shimamoto
authors.affiliation: Department of Cellular and Molecular Biology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tahara
authors.affiliation: Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurumizaka
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan. Electronic address: mtakata@house.rbc.kyoto-u.ac.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Takata
authors.affiliation: Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara 259-1193, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yabe
authors.affiliation: Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara 259-1193, Japan.
authors.forename: Miharu
authors.initials: M
authors.lastname: Yabe
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000235:genetics* / Q000473:pathology*; D052240:Fanconi Anemia Complementation Group L Protein / Q000378:metabolism; D005260:Female; D040461:Gene Components; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D011487:Protein Conformation; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D054875:Ubiquitination / Q000235:genetics
chemical_list: C513404:UBE2T protein, human; D044763:Ubiquitin-Conjugating Enzymes; C499908:FANCL protein, human; D052240:Fanconi Anemia Complementation Group L Protein