A unique chromosomal in-frame deletion identified among seven XP-C patients

• Verfasst von: Schubert, Steffen [VerfasserIn]
• Verfasst von: Gratchev, Alexei [VerfasserIn]
• Titel: A unique chromosomal in-frame deletion identified among seven XP-C patients
• Verf.angabe: Steffen Schubert, Petra Rieper, Andreas Ohlenbusch, Christina Seebode, Janin Lehmann, Alexei Gratchev and Steffen Emmert
• E-Jahr: 2016
• Jahr: 27 July 2016
• Umfang: 8 S.
• Fussnoten: Gesehen am 04.01.2018
• Titel Quelle: Enthalten in: Photodermatology, photoimmunology & photomedicine
• Ort Quelle: Oxford [u.a.] : Wiley-Blackwell, 1990
• Jahr Quelle: 2016
• Band/Heft Quelle: 32(2016), 5/6, Seite 276-283
• ISSN Quelle: 1600-0781
• DOI: doi:10.1111/phpp.12251
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: skin cancer
• Sach-SW: sun sensitivity
• Sach-SW: xeroderma pigmentosum
• Sach-SW: XP complementation group C
• Sach-SW: XPC
• K10plus-PPN: 1566859581

Abstract

Background The nucleotide excision repair (NER) pathway, defective in xeroderma pigmentosum (XP) patients, removes DNA photolesions in order to prevent carcinogenesis. Complementation group C (XP-C) is the most frequent group of XP patients worldwide. Methods We analyzed seven XP-C patients clinically and molecular-genetically applying: post-UV cell survival (MTT-assay), quantitative Real-time PCR, sequencing on chromosomal as well as cDNA level, and in silico interpretation of sequencing data. Results All cases displayed diminished post-UV cell survival as well as reduced XPC mRNA levels. Five homozygous and two heterozygous disease causing mutations were identified. A large chromosomal deletion of ~5.8 kb identified in XP174MA leads to an unique in frame deletion of XPC exon 2 and exon 3. In silico analysis revealed the deletion of 102 amino acids in the N-terminal part of XPC while leaving the C-terminal domain intact. The novel c.361delA mutation in XP168MA leads to a frameshift in exon 3 resulting in a premature stop codon 27 codons downstream of the deleted adenine. Conclusion Our analysis confirms that XP-C patients without increased sun sensitivity develop non-melanoma skin cancers earlier than sun-sensitive XP-C patients. Reduced cellular mRNA levels are characteristic for XP complementation group C and qRT-PCR represents a rapid diagnostic tool.