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Xeroderma pigmentosum-variant patients from America, Europe, and Asia

Authors
 Hiroki Inui  ;  Kyu-Seon Oh  ;  Carine Nadem  ;  Takahiro Ueda  ;  Sikandar G. Khan  ;  Ahmet Metin  ;  Engin Gozukara  ;  Steffen Emmert  ;  Hanoch Slor  ;  David B. Busch  ;  Carl C. Baker  ;  John J. DiGiovanna  ;  Deborah Tamura  ;  Cornelia S. Seitz  ;  Alexei Gratchev  ;  Wen Hao Wu  ;  Kee Yang Chung  ;  Hye Jin Chung  ;  Esther Azizi  ;  Roger Woodgate  ;  Thomas D. Schneider  ;  Kenneth H. Kraemer 
Citation
 JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol.128(8) : 2055-2068, 2008 
Journal Title
 JOURNAL OF INVESTIGATIVE DERMATOLOGY 
ISSN
 0022-202X 
Issue Date
2008
MeSH
Adolescent ; Adult ; Aged ; Asia ; Child ; Codon, Nonsense/genetics ; DNA-Directed DNA Polymerase/genetics* ; DNA-Directed DNA Polymerase/metabolism ; Europe ; Female ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Frameshift Mutation/genetics ; Humans ; Male ; Middle Aged ; Mutation/genetics* ; Mutation, Missense/genetics ; North America ; Pedigree ; RNA, Messenger/metabolism ; Xeroderma Pigmentosum/ethnology ; Xeroderma Pigmentosum/genetics* ; Xeroderma Pigmentosum/metabolism
Keywords
Adolescent ; Adult ; Aged ; Asia ; Child ; Codon, Nonsense/genetics ; DNA-Directed DNA Polymerase/genetics* ; DNA-Directed DNA Polymerase/metabolism ; Europe ; Female ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Frameshift Mutation/genetics ; Humans ; Male ; Middle Aged ; Mutation/genetics* ; Mutation, Missense/genetics ; North America ; Pedigree ; RNA, Messenger/metabolism ; Xeroderma Pigmentosum/ethnology ; Xeroderma Pigmentosum/genetics* ; Xeroderma Pigmentosum/metabolism
Abstract
Xeroderma pigmentosum-variant (XP-V) patients have sun sensitivity and increased skin cancer risk. Their cells have normal nucleotide excision repair, but have defects in the POLH gene encoding an error-prone polymerase, DNA polymerase eta (pol eta). To survey the molecular basis of XP-V worldwide, we measured pol eta protein in skin fibroblasts from putative XP-V patients (aged 8-66 years) from 10 families in North America, Turkey, Israel, Germany, and Korea. Pol eta was undetectable in cells from patients in eight families, whereas two showed faint bands. DNA sequencing identified 10 different POLH mutations. There were two splicing, one nonsense, five frameshift (3 deletion and 2 insertion), and two missense mutations. Nine of these mutations involved the catalytic domain. Although affected siblings had similar clinical features, the relation between the clinical features and the mutations was not clear. POLH mRNA levels were normal or reduced by 50% in three cell strains with undetectable levels of pol eta protein, indicating that nonsense-mediated message decay was limited. We found a wide spectrum of mutations in the POLH gene among XP-V patients in different countries, suggesting that many of these mutations arose independently.
Files in This Item:
T200800678.pdf Download
DOI
10.1038/jid.2008.48
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Chung, Kee Yang(정기양) ORCID logo https://orcid.org/0000-0003-3257-0297
Chung, Hye Jin(정혜진)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106927
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