Malfunction of Nuclease ERCC1-XPF Results in Diverse Clinical Manifestations and Causes Cockayne Syndrome, Xeroderma Pigmentosum, and Fanconi Anemia

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• 作者：Kazuya Kashiyama¹ ; ² ; ³ ; ¹⁶ ; Yuka Nakazawa² ; ⁴ ; ¹⁶ ; Daniela T. Pilz⁵ ; ¹⁶ ; Chaowan Guo² ; ⁴ ; ¹⁶ ; Mayuko Shimada² ; ⁴ ; Kensaku Sasaki² ; ⁴ ; Heather Fawcett⁶ ; Jonathan F. Wing⁶ ; Susan O. Lewin⁷ ; Lucinda Carr⁸ ; Tao-Sheng Li⁹ ; Koh-ichiro Yoshiura¹⁰ ; Atsushi Utani¹¹ ; Akiyoshi Hirano¹ ; Shunichi Yamashita³ ; ¹² ; Danielle Greenblatt¹³ ; Tiziana Nardo¹⁴ ; Miria Stefanini¹⁴ ; David McGibbon¹³ ; Robert Sarkany¹³ ; Hiva Fassihi¹³ ; Yoshito Takahashi¹⁵ ; Yuji Nagayama⁴ ; Norisato Mitsutake² ; ³ ; Alan R. Lehmann⁶ ; ¹⁷ ; ^{a.r.lehmann@sussex.ac.uk} ; Tomoo Ogi² ; ⁴ ; ¹⁷ ; ^{togi@nagasaki-u.ac.jp}
• 刊名：The American Journal of Human Genetics
• 出版年：2013
• 出版时间：2 May, 2013
• 年：2013
• 卷：92
• 期：5
• 页码：807-819
• 全文大小：1372 K

文摘

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¡ªCS, 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.