APC mutation and phenotypic spectrum of Singapore familial adenomatous polyposis patients
APC mutation and phenotypic spectrum of Singapore familial adenomatous polyposis patients
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DOI：
10.1038/sj.ejhg.5200397
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发表时间：
2000-01-01
影响因子：
5.2
通讯作者：
Cheah, PY
中科院分区：
文献类型：
--
作者：
Cao, X;Eu, KW;Cheah, PY
家族性腺瘤性息肉病(FAP)是一种由腺瘤性结肠息肉病(APC)基因突变引起的家族性结肠癌。虽然APC基因在高加索人群中得到了广泛的研究，但在中国人群中还没有被描述过。在本研究中，我们调查了以中国人为主的新加坡FAP家族的APC突变和表型谱。采用蛋白质截断试验(PTT)对28个无血缘关系的家系进行APC基因的种系突变筛查。在22个家系中发现了15个不同的突变，其中8个突变是1-11碱基缺失或插入，3个涉及整个外显子的缺失，4个是无义突变。其中9个突变，包括两个复杂的重排，是新的。包括3例新发病例在内的8个家系在1309密码子上有相同的(AAAGA)缺失，这表明与西方家庭一样，1309密码子也是新加坡FAP家族的突变热点。相比之下，我们没有在1061密码子上发现任何突变，这是西方人口的第二个热点。先天性视网膜色素上皮肥大(CHRPE)与指定的区域(密码子463至1387)一致相关，是唯一没有家族内变异的表型。除CHRPE外，FAP家族中结肠外表现的类型和频率的差异提示了修饰基因和环境因素的影响。
Familial adenomatous polyposis (FAP) is a familial form of colon cancer caused by mutation of the adenomatous polyposis coli (APC) gene. Although the APC gene has been extensively studied in the Caucasian population, it has not been previously described in the Chinese population. In the present study, we investigated APC mutation and phenotypic spectrum in the Singapore FAP families who are predominantly Chinese. The protein truncation test (PTT) was used to screen the entire APC gene for germline mutations in 28 unrelated families. Fifteen different mutations were identified in 22families, Eight mutations were 1-11 basepair deletions or insertions; three involved deletions of whole exons and four were nonsense mutations. Nine of the mutations, including two complex rearrangements, are novel. Eight families including three de novo cases have the same (AAAGA) deletion at codon 1309, indicating that like the Western families, codon 1309 is also the mutation 'hot spot' for Singapore FAP families. In contrast, we did not find any mutation in codon 1061, the second hot spot for the Western population. Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is consistently associated with the prescribed domain (codons 463 to 1387) and is the only phenotype with no intra-family variation. Other than CHRPE, differences in the type and frequency of extracolonic manifestations within the FAP families suggest the influence of modifying genes and environmental factors.