title: A unique chromosomal in-frame deletion identified among seven XP-C patients.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Schubert
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Rieper
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ohlenbusch
authors.affiliation: Clinic for Dermatology and Venereology, University Medical Center Rostock, Rostock, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Seebode
authors.affiliation: Clinic for Dermatology and Venereology, University Medical Center Rostock, Rostock, Germany.
authors.forename: Janin
authors.initials: J
authors.lastname: Lehmann
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center Heidelberg, Heidelberg, Germany.|Institute of Carcinogenesis, NN Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: Alexei
authors.initials: A
authors.lastname: Gratchev
authors.affiliation: Clinic for Dermatology and Venereology, University Medical Center Rostock, Rostock, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Emmert
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D002872:Chromosome Deletion; D002877:Chromosomes, Human / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C086984:XPC protein, human
keywords: XP complementation group C; XPC; skin cancer; sun sensitivity; xeroderma pigmentosum