Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis.
Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis.
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同义突变腺瘤性大肠杆菌Î486s 影响外显子剪接，并可能使患者易患腺瘤性大肠杆菌/mutY DNA 糖基化酶突变 — 阴性家族性腺瘤性息肉病
DOI：
10.3892/mmr.2018.9495
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发表时间：
2018-12
影响因子：
3.4
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Liu WQ;Dong J;Peng YX;Li WL;Yang J
家族性腺瘤性息肉病是一种常染色体显性遗传的结直肠癌。遗传学的最新进展表明，大多数FAP患者携带大肠腺瘤性息肉病（APC）和mutY DNA糖基化酶（MUTYH）基因的种系突变。然而，有FAP病史的大部分家族具有不可检测的致病性改变，称为APC/MUTYH突变阴性FAP。为了研究中国FAP患者APC和MUTYH基因的种系突变，招募了13名无关患者。通过基因测序，在6个个体中鉴定出APC的4个已知致病性改变（Lys 1061 LysfsTer 2、Glu 1309 AspfsTer 4、Arg 283 Ter和Ser 1196 Ter）和MUTYH的2个新的疾病相关致病性突变（Tyr 152 Ter和Ter 522 Gly）。对于不存在致病性改变的样品，使用生物信息学工具和数据库分析错义、同义和内含子突变的功能效应。生物信息学预测提示APC基因Tyr 486 Tyr（APC → 486 s）突变可能是一种致病性多态性，并可能导致APC基因外显子跳读。进行了杂合微基因分析，证实了同义单核苷酸多态性APC 486 s诱导APC中外显子12跳跃的主要剪接缺陷。本研究的数据表明，同义多态性APC 486 s是一个潜在的致病性改变，使APC/MUTYH突变阴性患者易患FAP。
Familial adenomatous polyposis (FAP) is an autosomal dominant-inherited colorectal cancer. Recent advances in genetics have indicated that the majority of patients with FAP carry germline mutations of the adenomatous polyposis coli (APC) and mutY DNA glycosylase (MUTYH) genes. However, a large subset of families with a history of FAP have undetectable pathogenic alterations, termed APC/MUTYH mutation-negative FAP. To investigate the germline mutations in the APC and MUTYH genes in Chinese patients with FAP, 13 unrelated patients were enrolled. Through genetic sequencing, four known pathogenic alterations (Lys1061LysfsTer2, Glu1309AspfsTer4, Arg283Ter and Ser1196Ter) of APC and two novel disease-associated pathogenic mutations (Tyr152Ter and Ter522Gly) in MUTYH were identified in six individuals. For samples that did not present with pathogenic alterations, the functional effects of missense, synonymous and intronic mutations were analyzed using bioinformatics tools and databases. Bioinformatics prediction suggested that the synonymous mutation Tyr486Tyr in APC (APC∆486s) was likely a disease-causing polymorphism and may have induced the exon skipping of APC. A hybrid mini-gene assay was performed, which confirmed that the synonymous single nucleotide polymorphism APC∆486s induced major splicing defects with skipping of exon 12 in APC. The data of the present study suggested that the synonymous polymorphism APC∆486s was a potential pathogenic alteration that predisposed APC/MUTYH mutation-negative patients to FAP.
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影响因子：
14.9
作者：
Ramensky, V;Bork, P;Sunyaev, S
通讯作者：
Sunyaev, S
影响因子：
64.5
作者：
GRODEN, J;THLIVERIS, A;WHITE, R
通讯作者：
WHITE, R
影响因子：
14.9
作者：
Cartegni, L;Wang, JH;Krainer, AR
通讯作者：
Krainer, AR
DOI：
10.1016/j.bbapap.2009.02.014
发表时间：
2009-05
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Fung KL;Gottesman MM
通讯作者：
Gottesman MM
影响因子：
7
作者：
Ng, PC;Henikoff, S
通讯作者：
Henikoff, S