Mamrak Nicholas E, Shimamura Akiko, Howlett Niall G
Department of Cell and Molecular Biology, University of Rhode Island, 120 Flagg Road, Kingston, RI 02881, United States.
Dana-Farber Cancer Institute/Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, United States.
Blood Rev. 2017 May;31(3):93-99. doi: 10.1016/j.blre.2016.10.002. Epub 2016 Oct 13.
Fanconi anemia (FA) is a rare autosomal and X-linked genetic disease characterized by congenital abnormalities, progressive bone marrow failure (BMF), and increased cancer risk during early adulthood. The median lifespan for FA patients is approximately 33years. The proteins encoded by the FA genes function together in the FA-BRCA pathway to repair DNA damage and to maintain genome stability. Within the past two years, five new FA genes have been identified-RAD51/FANCR, BRCA1/FANCS, UBE2T/FANCT, XRCC2/FANCU, and REV7/FANCV-bringing the total number of disease-causing genes to 21. This review summarizes the discovery of these new FA genes and describes how these proteins integrate into the FA-BRCA pathway to maintain genome stability and critically prevent early-onset BMF and cancer.
范可尼贫血(FA)是一种罕见的常染色体和X连锁遗传病,其特征为先天性异常、进行性骨髓衰竭(BMF)以及成年早期癌症风险增加。FA患者的中位寿命约为33岁。FA基因编码的蛋白质在FA-BRCA通路中共同发挥作用,以修复DNA损伤并维持基因组稳定性。在过去两年中,已鉴定出五个新的FA基因——RAD51/FANCR、BRCA1/FANCS、UBE2T/FANCT、XRCC2/FANCU和REV7/FANCV,使致病基因总数达到21个。本综述总结了这些新FA基因的发现,并描述了这些蛋白质如何整合到FA-BRCA通路中以维持基因组稳定性,并严格预防早发性BMF和癌症。