title: Malfunction of nuclease ERCC1-XPF results in diverse clinical manifestations and causes Cockayne syndrome, xeroderma pigmentosum, and Fanconi anemia.
abstract: Cockayne syndrome (CS) is a genetic disorder characterized by developmental abnormalities and photodermatosis resulting from the lack of transcription-coupled nucleotide excision repair, which is responsible for the removal of photodamage from actively transcribed genes. To date, all identified causative mutations for CS have been in the two known CS-associated genes, ERCC8 (CSA) and ERCC6 (CSB). For the rare combined xeroderma pigmentosum (XP) and CS phenotype, all identified mutations are in three of the XP-associated genes, ERCC3 (XPB), ERCC2 (XPD), and ERCC5 (XPG). In a previous report, we identified several CS cases who did not have mutations in any of these genes. In this paper, we describe three CS individuals deficient in ERCC1 or ERCC4 (XPF). Remarkably, one of these individuals with XP complementation group F (XP-F) had clinical features of three different DNA-repair disorders--CS, XP, and Fanconi anemia (FA). Our results, together with those from Bogliolo et al., who describe XPF alterations resulting in FA alone, indicate a multifunctional role for XPF.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kashiyama
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nakazawa
authors.forename: Daniela T
authors.initials: DT
authors.lastname: Pilz
authors.forename: Chaowan
authors.initials: C
authors.lastname: Guo
authors.forename: Mayuko
authors.initials: M
authors.lastname: Shimada
authors.forename: Kensaku
authors.initials: K
authors.lastname: Sasaki
authors.forename: Heather
authors.initials: H
authors.lastname: Fawcett
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Wing
authors.forename: Susan O
authors.initials: SO
authors.lastname: Lewin
authors.forename: Lucinda
authors.initials: L
authors.lastname: Carr
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
authors.forename: Koh-ichiro
authors.initials: K
authors.lastname: Yoshiura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Utani
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hirano
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Danielle
authors.initials: D
authors.lastname: Greenblatt
authors.forename: Tiziana
authors.initials: T
authors.lastname: Nardo
authors.forename: Miria
authors.initials: M
authors.lastname: Stefanini
authors.forename: David
authors.initials: D
authors.lastname: McGibbon
authors.forename: Robert
authors.initials: R
authors.lastname: Sarkany
authors.forename: Hiva
authors.initials: H
authors.lastname: Fassihi
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagayama
authors.forename: Norisato
authors.initials: N
authors.lastname: Mitsutake
authors.forename: Alan R
authors.initials: AR
authors.lastname: Lehmann
authors.forename: Tomoo
authors.initials: T
authors.lastname: Ogi
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003057:Cockayne Syndrome / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005199:Fanconi Anemia / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D017422:Sequence Analysis, DNA; D014983:Xeroderma Pigmentosum / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C095888:xeroderma pigmentosum group F protein; C071447:ERCC1 protein, human; D004720:Endonucleases