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Kralund HH, Ousager L, Jaspers NG, et al. Xeroderma Pigmentosum-Trichothiodystrophy overlap patient with novel XPD/ERCC2 mutation. Rare Dis. 2013;1:e24932doi: 10.4161/rdis.24932.
Kralund, H. H., Ousager, L., Jaspers, N. G., Raams, A., Pedersen, E. B., Gade, E., & Bygum, A. (2013). Xeroderma Pigmentosum-Trichothiodystrophy overlap patient with novel XPD/ERCC2 mutation. Rare diseases (Austin, Tex.), 1e24932. https://doi.org/10.4161/rdis.24932
Kralund, Henrik H, et al. "Xeroderma Pigmentosum-Trichothiodystrophy overlap patient with novel XPD/ERCC2 mutation." Rare diseases (Austin, Tex.) vol. 1 (2013): e24932. doi: https://doi.org/10.4161/rdis.24932
Kralund HH, Ousager L, Jaspers NG, Raams A, Pedersen EB, Gade E, Bygum A. Xeroderma Pigmentosum-Trichothiodystrophy overlap patient with novel XPD/ERCC2 mutation. Rare Dis. 2013 May 06;1:e24932. doi: 10.4161/rdis.24932. eCollection 2013. PMID: 25002996; PMCID: PMC3916142.
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Rare Dis. 2013 May 06;1:e24932. doi: 10.4161/rdis.24932. eCollection 2013.

Xeroderma Pigmentosum-Trichothiodystrophy overlap patient with novel XPD/ERCC2 mutation.

Rare diseases (Austin, Tex.)

Henrik H Kralund, Lilian Ousager, Nicolaas G Jaspers, Anja Raams, Erling B Pedersen, Else Gade, Anette Bygum

Affiliations

  1. Department of Dermatology and Allergy Centre; Odense University Hospital; Odense, Denmark.
  2. Department of Clinical and Medical Genetics; Odense University Hospital; Odense, Denmark.
  3. Department of Genetics; Erasmus Medical Center; Rotterdam, Netherlands.
  4. Departments of Medical Research and Medicine; University of Aarhus and Holstebro Hospital; Aarhus, Denmark.
  5. Department of Ophthalmology; Odense University Hospital; Odense, Denmark.

PMID: 25002996 PMCID: PMC3916142 DOI: 10.4161/rdis.24932

Abstract

Xeroderma Pigmentosum (XP), Trichothiodystrophy (TTD) and Cockayne Syndrome (CS) are rare, recessive disorders caused by mutational defects in the Nucleotide Excision Repair (NER) pathway and/or disruption of basic cellular DNA transcription. To date, a multitude of mutations in the XPD/ERCC2 gene have been described, many of which give rise to NER- and DNA transcription related diseases, which share certain diagnostic features and few overlap patients have been described. Despite increasing understanding of the roles of XPD/ERCC2 in mammalian cells, there is still weak predictability of somatic outcome from many of these mutations. We demonstrate a patient, believed to represent an overlap between XP and TTD/CS. In addition to other organ dysfunctions, the young man presented with Photosensitivity, Ichthyosis, Brittle hair, Impaired physical and mental development, Decreased fertility and Short stature (PIBIDS) suggestive of TTD, but lacking the almost patognomonic "tiger tail" banding of the hair under polarized light. Additionally, he developed basal cell carcinoma aged 28, as well as adult onset kidney failure, features normally not associated with TTD but rather XP/CS. His freckled appearance also suggested XP, but fibroblast cultures only demonstrated x2 UV-sensitivity with expected NER and TFIIH-activity decrease. Genetic sequencing of the XPD/ERCC2 gene established the patient as heterozygote compound with a novel, N-terminal Y18H mutation and a known C-terminal (TTD) mutation, A725P. The possible interplay between gene products and the patient phenotype is discussed.

Keywords: Trichothiodystrophy; XPD-gene; novel mutation; overlap syndrome; xeroderma pigmentosum

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