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.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Child
  • Child, Preschool
  • Fanconi Anemia / genetics*
  • Fanconi Anemia / pathology*
  • Fanconi Anemia Complementation Group L Protein / metabolism
  • Female
  • Gene Components
  • Genotype
  • Humans
  • Japan
  • Male
  • Models, Molecular*
  • Molecular Sequence Data
  • Mutation, Missense / genetics*
  • Pedigree
  • Protein Conformation
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Ubiquitin-Conjugating Enzymes / chemistry
  • Ubiquitin-Conjugating Enzymes / genetics*
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Ubiquitination / genetics

Substances

  • UBE2T protein, human
  • Ubiquitin-Conjugating Enzymes
  • FANCL protein, human
  • Fanconi Anemia Complementation Group L Protein