Clinical utility gene card for: poikiloderma with neutropenia
Clinical utility gene card for: poikiloderma with neutropenia
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临床实用基因卡：皮肤异色症伴中性粒细胞减少症
DOI：
10.1038/ejhg.2012.298
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发表时间：
2013
影响因子：
5.2
通讯作者：
Y. Sznajer
中科院分区：
文献类型：
--
作者：
L. Larizza;Gloria Negri;E. Colombo;L. Volpi;Y. Sznajer
到目前为止，在37名接受分子遗传学检测的PN患者中检测到19种不同的C16 orf 57突变。在这37例患者中，31例（84%）携带纯合突变，而其他6例为复合杂合突变。3所有鉴定的突变导致产生截短的和最可能无功能的C16 orf 57蛋白。C16 orf 57是剪接装置的生物发生所必需的30-50核酸外切酶。4，5已经鉴定了几类突变，在此按患病率递减的顺序列出：无义突变（c. 232C> T，c. 243G> A，c. 258T> A，c. 267T> A，c. 415 C> T，c. 541 C> T，c. 673 C> T）;小框外缺失（c. 176_177delG，c. 179delC，c. 489_492del4角496delA，c. 531delA，c. 683_8931del12）;和剪接改变，包括在典型剪接点或剪接位点共有序列处的取代（c. 265 ° 2T> G，c. 26601G> A，c. 45002A> G，c. 502A> G，c. 50412A> C，c. 6931G> T）。2，3，6-10尚未发现错义突变; c. 502 A> G可以归类为剪接改变，因为它导致从成熟C16 orf 57 -001转录物切除第四外显子。2
So far, 19 different C16orf57 mutations have been detected in 37 PN patients subjected to molecular-genetic testing. Of these 37 patients, 31 (84%) carry homozygous mutations, whereas the other six are compound heterozygous. 3 All identified mutations lead to the generation of truncated and most likely non-functional C16orf57 protein. C16orf57 is a 30–50 exonuclease essential for the biogenesis of the splicing apparatus. 4, 5 Several classes of mutations have been identified, listed here in order of decreasing prevalence: nonsense mutations (c. 232C> T, c. 243G> A, c. 258T> A, c. 267T> A, c. 415C> T, c. 541C> T, c. 673C> T); small out-of-frame deletions (c. 176_177delG, c. 179delC, c. 489_492del4, c. 496delA, c. 531delA, c. 683_893þ 1del12); and splicing alterations, including substitutions at canonical splice junctions or at splice-site consensus sequences (c. 265þ 2T> G, c. 266À1G> A, c. 450À2A> G, c. 502A> G, c. 504À2A> C, c. 693þ 1G> T). 2, 3, 6–10 No missense mutations have yet been found; c. 502A> G can be categorised as a splicing alteration because it leads to the excision of the fourth exon from the mature C16orf57-001 transcript. 2