title: A novel XPC pathogenic variant detected in archival material from a patient diagnosed with Xeroderma Pigmentosum: a case report and review of the genetic variants reported in XPC.
abstract: The disease Xeroderma Pigmentosum (XP) is genetically heterogeneous and defined by pathogenic variants (formerly termed mutations) in any of eight different genes. Pathogenic variants in the XPC gene are the most commonly observed in US patients. Moreover, pathogenic variants in just four of the genes, XPA, XPC, XPD/ERCC2 and XPV/POLH account for 91% of all XP cases worldwide. In the current study, we describe the clinical, histopathologic, molecular genetic, and pathophysiological features of a 19-year-old female patient clinically diagnosed with XP as an infant. Analysis of archival material reveals a novel variation of a 13 base pair deletion in XPC exon 14 and a previously reported A>C missense pathogenic variant in the proximal splice site for XPC exon 6. Both variations induce frameshifts most likely leading to a truncated XPC protein product. Quantitative RT-PCR also revealed reduced mRNA levels in the archived specimen. Analysis of the XPA, XPD/ERCC2 and XPV/POLH genes in the current specimen failed to reveal pathologic variants. All previously reported pathogenic variants, polymorphisms and known amino acid changes for the XPC gene are compiled and described in the current nomenclature. Given the relative ease of screening for genetic variation and the potential role for such variation in human disease, a proposal for screening appropriate archival materials for alterations in the four most prevalent XP genes is presented.
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9072, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Rivera-Begeman
authors.forename: Lisa D
authors.initials: LD
authors.lastname: McDaniel
authors.forename: Roger A
authors.initials: RA
authors.lastname: Schultz
authors.forename: Errol C
authors.initials: EC
authors.lastname: Friedberg
mesh_terms: D000328:Adult; D001109:Archives; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014983:Xeroderma Pigmentosum / Q000175:diagnosis* / Q000235:genetics; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C086984:XPC protein, human; D051759:Xeroderma Pigmentosum Group D Protein