Molecular analysis of the APC gene in 71 Israeli families: 17 novel mutations.
Molecular analysis of the APC gene in 71 Israeli families: 17 novel mutations.
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DOI：
10.1002/humu.9037
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发表时间：
2002-06-01
期刊：
影响因子：
3.9
通讯作者：
Orr-Urtreger, Avi
中科院分区：
文献类型：
--
作者：
Gavert, Nancy;Yaron, Yuval;Orr-Urtreger, Avi
家族性腺瘤性息肉病（FAP）是由APC基因的种系突变引起的。这项研究包括71个以色列家庭的APC基因的分子分析。通过外显子15的蛋白质截短试验（PTT）进行分析，如果阴性，则通过外显子1至14的直接测序进行分析。36例（50.7%）先证者存在突变。突变检测率取决于转介模式，例如遗传性癌症服务中心转介的40名先证者中，突变检测率为70%，而其他胃肠病学家转介的31名先证者中，突变检测率明显较低（25.8%）。在检测到的36个突变中，21个位于外显子15内，13个位于外显子1至14内，2个为内含子9和14的新描述的剪接突变。第9外显子的突变比例较高（6/36），其中5个是新发现的。我们在这里总共描述了17个新的突变。在以色列的两个主要种族群体中，德系犹太人和非德系犹太人，APC基因内的突变检测率或突变分布没有显著差异。在这些人群中均未检测到创始者突变。我们的数据证实，在遗传性结肠癌专业临床服务机构转介的患者中，预期检出率较高。这些结果进一步强调了对所有外显子和外显子/内含子边界进行完整分析的重要性，以便在疑似FAP的患者中实现最大的检出率。
Familial adenomatous polyposis (FAP) is caused by germline mutations in the APC gene. This study included 71 Israeli families referred for molecular analysis of the APC gene. Analysis was performed by the protein truncation test (PTT) of exon 15, and if negative, by direct sequencing of exon 1 to 14. Mutations were found in 36 (50.7%) probands. Mutation detection rates depended on the pattern of referral, such that among the 40 probands referred from the Service for Hereditary Cancer the mutation detection rate was 70%, whereas among the 31 probands referred by other gastroenterologists detection rate was significantly lower (25.8%). Of the 36 mutations detected, 21 were within exon 15, 13 within exons 1 to 14 and 2 were newly-described splicing mutations in introns 9 and 14. A relatively high proportion of the mutations was detected in exon 9 (6/36), five of them newly described. Altogether, we describe here 17 new mutations. Within the two major ethnic groups in Israel, patients of Ashkenazi and non-Ashkenazi origin, there was no significant differences in the mutation detection rate or the distribution of mutations within the APC gene. No founder mutation was detected in any of these populations. Our data confirm that higher detection rates may be expected in patients referred by clinical services specializing in hereditary colon cancer. These results further underscore the importance of complete analysis of all exons and exon/intron boundaries, in order to achieve maximal detection rate in patients suspected of FAP.