APC gene mutations causing familial adenomatous polyposis in Polish patients
APC gene mutations causing familial adenomatous polyposis in Polish patients
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DOI：
10.1007/bf03195640
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发表时间：
2008-01-01
影响因子：
2.4
通讯作者：
Slomski, Ryszard
中科院分区：
文献类型：
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作者：
Plawski, Andrzej;Slomski, Ryszard
家族性腺瘤性息肉病（FAP）是一种众所周知的以消化系统肿瘤为特征的遗传性疾病。在患者的结肠和直肠中会出现成千上万的息肉。息肉发生的次数和时间具有高度的异质性。FAP的发生与APC肿瘤抑制基因的突变有关，该基因于1991年被描述。从那时起，已经进行了许多研究来分析突变在个体群体中的分布，并确定基因的功能和FAP的诊断方法。在这里，我们研究了APC基因在300个不相关的波兰FAP家族中发生的小突变和大重排。在164个家族中发现了97个突变。在这些突变中，80个是小突变，其中58个是首次在波兰人群中发现的小突变（42个是新的，16个是先前描述的）。10%的波兰人突变c.3927_3931delAAAGA的频率增加。在29个家庭中发现了17个大规模的重新安排。在这些重新安排中，有8次重复重新安排发生在20个家庭中。快速分子诊断FAP的一个问题是APC基因突变的高度异质性。看来，多重连接依赖探针扩增试验和使用筛选方法在外显子15和外显子14、9、11、13、5和3的5'端搜索小突变，有助于提高波兰患者FAP的分子诊断。
Familial adenomatous polyposis (FAP) is a well-known hereditary condition characterised by alimentary System tumours. Tens to thousands of polyps occur in the colon and rectum of the patients. There is a high heterogeneity with regard to the number and time of the occurrence of polyps. The occurrence of FAP is associated with mutations in the APC tumour suppressor gene, which was described in 1991. Since then, many studies have been done to analyse the distribution of mutations in individual populations and to determine the function of the gene and a diagnostic approach to FAP. Here the APC gene vas studied with respect to the Occurrence of small Mutations and large rearrangements in 300 unrelated Polish FAP families. Ninety-seven mutations were identified in 164 families. Out Of these mutations, 80 were small mutations, including 58 small Mutations that were first identified in the Polish population (42 novel and 16 described previously). An increased frequency of Mutation c.3927_3931delAAAGA was observed in 10% of the Polish group. Seventeen large rearrangements were found ill 29 families. Out of those rearrangements, 8 repeat rearrangements occurred ill 20 families. A problem in fast molecular diagnostics of FAP is a high heterogeneity Of Mutations in the APC gene. It seems that a multiplex ligation-dependent probe amplification test and searching for small mutations by the use of screening methods at the 5' end of exon 15 and exons 14, 9, 11, 13, 5, and 3, help to improve the molecular diagnostics of FAP in Polish patients.