title: Xeroderma pigmentosum-variant patients from America, Europe, and Asia.
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.
authors: DNA Repair Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892-4258, USA.
authors: Hiroki
authors: H
authors: Inui
authors: Kyu-Seon
authors: KS
authors: Oh
authors: Carine
authors: C
authors: Nadem
authors: Takahiro
authors: T
authors: Ueda
authors: Sikandar G
authors: SG
authors: Khan
authors: Ahmet
authors: A
authors: Metin
authors: Engin
authors: E
authors: Gozukara
authors: Steffen
authors: S
authors: Emmert
authors: Hanoch
authors: H
authors: Slor
authors: David B
authors: DB
authors: Busch
authors: Carl C
authors: CC
authors: Baker
authors: John J
authors: JJ
authors: DiGiovanna
authors: Deborah
authors: D
authors: Tamura
authors: Cornelia S
authors: CS
authors: Seitz
authors: Alexei
authors: A
authors: Gratchev
authors: Wen Hao
authors: WH
authors: Wu
authors: Kee Yang
authors: KY
authors: Chung
authors: Hye Jin
authors: HJ
authors: Chung
authors: Esther
authors: E
authors: Azizi
authors: Roger
authors: R
authors: Woodgate
authors: Thomas D
authors: TD
authors: Schneider
authors: Kenneth H
authors: KH
authors: Kraemer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001208:Asia; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D005060:Europe; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D016368:Frameshift Mutation / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009656:North America; D010375:Pedigree; D012333:RNA, Messenger / Q000378:metabolism; D014983:Xeroderma Pigmentosum / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D000099270:Y-Family DNA Polymerases
chemical_list: D018389:Codon, Nonsense; D004259:DNA-Directed DNA Polymerase; D012333:RNA, Messenger; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases