Xeroderma Pigmentosum, Cockayne Syndrome, Trichothiodystrophy – Defects in DNA Repair and Carcinogenesis

Emmert, Steffen

doi:10.1002/9783527627523.ch25

Cited by 4 publications

(2 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We tested all cells in the presence of 1 m m caffeine (data not shown) and without caffeine at a density of 5000 and 7500 cells/well. A reduction in post‐UV cell survival only in the presence of caffeine would be indicative for XP variant cells defective in polymerase eta . All patient cells showed a reduced post‐UV cell survival at a dose of 30 J/m 2 UVC compared with wild‐type fibroblasts.…”

Section: Resultsmentioning

confidence: 95%

See 1 more Smart Citation

Molecular genetic analysis of 16 XP‐C patients from Germany: environmental factors predominately contribute to phenotype variations

Schäfer

Hofmann

Gratchev

et al. 2012

Experimental Dermatology

Self Cite

View full text Add to dashboard Cite

Patients belonging to xeroderma pigmentosum (XP) complementation group C comprise one-third of all XP patients. Only four major reports compiled larger groups of XP-C patients from southern Europe (12 pts), North America (16 pts) and Africa (14 and 56 pts) as well as their genetic background (46 XPC mutations). We identified 16 XP-C patients from Germany. Interestingly, only five patients exhibited severe sun sensitivity. The mean age of XP diagnosis was 9.4 years, and the median age of the first skin cancer was 7 years. Neurological symptoms were absent in all but two patients. Primary fibroblasts from all 16 patients showed reduced post-UV cell survival (mean: 50% vs 93% in normal cells) and reduced reactivation of an UV-treated luciferase reporter gene (mean: 6.4% vs 30.7% in normal cells). XPC mRNA expression was also greatly reduced compared with normal cells (mean: 14.3%; range 8.3-25.7%) except in XP47MA (274.1%). All patients carried homozygous XPC mutations. Four mutations have been described previously: c.1747_1748delTG (found in 4/16), c.567 C>T (4/16), c.1839 C>T (1/16) and a complex insertion/deletion mutation in exon 9 (1/16). The novel frameshift mutations c.446_447delAG (2/16), c.1525insA (1/16) and c.2271delC (1/16) lead to truncated XPC proteins as does the novel nonsense mutation c.843C>T (1/16). XP47MA carries an interesting mutation (c.2538_2540delATC; p.Ile812del) resulting in an in-frame single amino acid deletion. This mutation results in a classical XP phenotype, a non-functional XPC protein, but elevated XPC mRNA expression. Our study indicates that extrinsic factors may contribute to XP-C symptom severity due to nonsense-mediated message decay.

show abstract

Section: Resultsmentioning

confidence: 95%

“…Accordingly, XP patients can be assigned to seven complementation groups, XP‐A to XP‐G, depending on the mutated gene. In addition, a XP variant form exists which is caused by mutations in the gene coding for DNA polymerase eta whose gene product allows for error‐free translesional synthesis, for example across UV photoproducts .…”

Section: Introductionmentioning

confidence: 99%