Genotype-phenotype correlations in attenuated adenomatous polyposis coli
Genotype-phenotype correlations in attenuated adenomatous polyposis coli
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DOI：
10.1086/301883
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发表时间：
1998-06-01
影响因子：
9.8
通讯作者：
Bapat, B
中科院分区：
文献类型：
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作者：
Soravia, C;Berk, T;Bapat, B
肿瘤抑制基因APC的生殖系突变与家族性腺瘤性息肉病（FAP）的一种变异-减毒腺瘤性结肠息肉病（AAPC）有关。AAPC是公认的发生40年）。本研究的目的是评估AAPC家族的基因型-表型相关性。通过蛋白质截短试验（PTT），从11例AAPC激酶患者中筛选出APC基因的全部编码区，并分析其表型差异。在7种激酶中发现了5种新的生殖系APC突变。突变位于APC基因的三个不同区域：（1）在跨越外显子4和5的5'端，（2）在外显子9内，和（3）在基因的3'远端。结直肠腺瘤数量的变异性在区域1突变的个体中最明显，并且上消化道表现在他们中更严重。在区域2或区域3突变的个体中，腺瘤的平均数量往往低于区域1突变的个体，尽管诊断时的年龄相似。在所有AAPC激酶中，观察到右侧结直肠腺瘤和直肠息肉保留占优势。在这些肾脏中发现了Na硬纤维瘤。我们的数据表明，在AAPC家族中，APC突变的位置可以部分预测特定的表型表达。这将有助于在设计定制的临床管理协议，在这个子集的9;AP患者。
Germ-line mutations of the tumor suppressor APC are implicated in attenuated adenomatous polyposis coli (AAPC), a variant of familial adenomatous polyposis (FAP). AAPC is recognized by the occurrence of 40 years). The aim of this study was to assess genotype-phenotype correlations in AAPC families. By protein-truncation test (PTT) assay, the entire coding region of the APC gene was screened in affected individuals from 11 AAPC kindreds,and their phenotypic differences were examined. Five novel germ-line APC mutations were identified in seven kindreds. Mutations were located in three different regions of the APC gene: (1) at the 5' end spanning exons 4 and 5, (2) within exon 9, and (3) at the 3' distal end of the gene. Variability in the number of colorectal adenomas was most apparent in individuals with mutations in region 1, and upper-gastrointestinal manifestations were more severe in them. In individuals with mutations in either region 2 or region 3, the average number of adenomas tended to be lower than those in individuals with mutations in region 1, although age at diagnosis was similar. In all AAPC kindreds, a predominance of right-sided colorectal adenomas and rectal polyp sparing was observed. Na desmoid tumors were found in these kindreds. Our data suggest that, in AAPC families, the location of the APC mutation may partially predict specific phenotypic expression. This should help in the design of tailored clinical-management protocols in this subset of 9;AP patients.