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

Nicolaas G.J. Jaspers, Anja Raams, Margherita Cirillo Silengo, Nils Wijgers, Laura J. Niedernhofer, Andria Rasile Robinson, Giuseppina Giglia-Mari, Deborah Hoogstraten, Wim J. Kleijer, Jan H.J. Hoeijmakers, Wim Vermeulen

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)457-466
Number of pages10
JournalAmerican Journal of Human Genetics
Volume80
Issue number3
DOIs
StatePublished - Mar 2007

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this

    Jaspers, N. G. J., Raams, A., Silengo, M. C., Wijgers, N., Niedernhofer, L. J., Robinson, A. R., Giglia-Mari, G., Hoogstraten, D., Kleijer, W. J., Hoeijmakers, J. H. J., & Vermeulen, W. (2007). 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. American Journal of Human Genetics, 80(3), 457-466. https://doi.org/10.1086/512486