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To date, different mutations have been reported that result in a complete deficiency, including: two deletions (295–298delTCAT and 1897delC), one splice-site mutation (IVS14+IG>A), four missense mutations (85T>C, 703C>T, 2657G>A, and 2983 G>T), a deletion of two nucleotides (1039–1040delTG), and the point mutations P86L, S201R, S492L, D949V and H978R [13]. The 85T>C mutation might be a common polymorphism, although functional analysis of a recombinantly expressed human protein carrying the 85T>C mutation showed no significant residual mutant enzyme activity [10,14]. An in-depth discussion of the clinical import of DPD can be found in a number of review articles, and two examples are provided in Refs. [37,38], which discuss the role of DPD in cancer therapy with 5FU |
» 搶金幣啦!回帖就可以得到:
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您是不是把一篇DPD的綜述一點(diǎn)點(diǎn)貼呀。 目前已報(bào)道有多個(gè)突變導(dǎo)致完全功能缺失,這些突變有:兩個(gè)缺失突變(295–298delTCAT and 1897delC),一個(gè)剪接位點(diǎn)突變(IVS14+IG>A),4個(gè)錯(cuò)義突變(85T>C, 703C>T, 2657G>A, and 2983 G>T),一個(gè)兩個(gè)核苷酸的缺失突變(1039–1040delTG)和幾個(gè)點(diǎn)突變P86L, S201R, S492L, D949V and H978R。85T>C突變可能是一個(gè)比較普遍的多態(tài)性,但攜帶85T>C突變的重組人DPD蛋白并沒有明顯的突變酶的活性殘余。大量綜述已經(jīng)深入討論了DPD的重要臨床作用,文獻(xiàn)37,38中就有兩個(gè)例子,這兩篇綜述討論了DPD在5FU治療癌癥中的作用。 |
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