Malfunction of nuclease ERCC1-XPF results in diverse clinical manifestations and causes Cockayne syndrome, xeroderma pigmentosum, and Fanconi anemia

Am J Hum Genet. 2013 May 2;92(5):807-19. doi: 10.1016/j.ajhg.2013.04.007. Epub 2013 Apr 25.


Cockayne syndrome (CS) is a genetic disorder characterized by developmental abnormalities and photodermatosis resulting from the lack of transcription-coupled nucleotide excision repair, which is responsible for the removal of photodamage from actively transcribed genes. To date, all identified causative mutations for CS have been in the two known CS-associated genes, ERCC8 (CSA) and ERCC6 (CSB). For the rare combined xeroderma pigmentosum (XP) and CS phenotype, all identified mutations are in three of the XP-associated genes, ERCC3 (XPB), ERCC2 (XPD), and ERCC5 (XPG). In a previous report, we identified several CS cases who did not have mutations in any of these genes. In this paper, we describe three CS individuals deficient in ERCC1 or ERCC4 (XPF). Remarkably, one of these individuals with XP complementation group F (XP-F) had clinical features of three different DNA-repair disorders--CS, XP, and Fanconi anemia (FA). Our results, together with those from Bogliolo et al., who describe XPF alterations resulting in FA alone, indicate a multifunctional role for XPF.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cockayne Syndrome / enzymology
  • Cockayne Syndrome / genetics*
  • Cockayne Syndrome / pathology
  • DNA Primers / genetics
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Fanconi Anemia / enzymology
  • Fanconi Anemia / genetics*
  • Fanconi Anemia / pathology
  • Fatal Outcome
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Molecular Sequence Data
  • Phenotype*
  • Sequence Analysis, DNA
  • Xeroderma Pigmentosum / enzymology
  • Xeroderma Pigmentosum / genetics*
  • Xeroderma Pigmentosum / pathology


  • DNA Primers
  • DNA-Binding Proteins
  • xeroderma pigmentosum group F protein
  • ERCC1 protein, human
  • Endonucleases