First reported patient with human ERCC1 deficiency has cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure

Am J Hum Genet. 2007 Mar;80(3):457-66. doi: 10.1086/512486. Epub 2007 Jan 29.


Nucleotide excision repair (NER) is a genome caretaker mechanism responsible for removing helix-distorting DNA lesions, most notably ultraviolet photodimers. Inherited defects in NER result in profound photosensitivity and the cancer-prone syndrome xeroderma pigmentosum (XP) or two progeroid syndromes: Cockayne and trichothiodystrophy syndromes. The heterodimer ERCC1-XPF is one of two endonucleases required for NER. Mutations in XPF are associated with mild XP and rarely with progeria. Mutations in ERCC1 have not been reported. Here, we describe the first case of human inherited ERCC1 deficiency. Patient cells showed moderate hypersensitivity to ultraviolet rays and mitomycin C, yet the clinical features were very severe and, unexpectedly, were compatible with a diagnosis of cerebro-oculo-facio-skeletal syndrome. This discovery represents a novel complementation group of patients with defective NER. Further, the clinical severity, coupled with a relatively mild repair defect, suggests novel functions for ERCC1.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics
  • Animals
  • Brain / abnormalities*
  • Cells, Cultured
  • Craniofacial Abnormalities / genetics*
  • DNA Repair / genetics*
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / genetics
  • Developmental Disabilities / genetics
  • Endonucleases / deficiency*
  • Endonucleases / genetics
  • Eye Abnormalities / genetics*
  • Fatal Outcome
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / radiation effects
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Polymerase Chain Reaction
  • Skin / cytology
  • Syndrome


  • DNA-Binding Proteins
  • ERCC1 protein, human
  • Endonucleases
  • Ercc1 protein, mouse