Novel germline mutations in the APC gene and their phenotypic spectrum in familial adenomatous polyposis kindreds
Novel germline mutations in the APC gene and their phenotypic spectrum in familial adenomatous polyposis kindreds
复制标题
家族性腺瘤性息肉病家族中 APC 基因的新种系突变及其表型谱
作者：
Corinne Walon;A. Kartheuser;G. Michils;M. Smaers;N. Lannoy;P. Ngounou;Guy Mertens;C. Verellen‐Dumoulin
摘要在45例家族性腺瘤性息肉病（FAP）患者APC筛查中发现的23个种系突变中，我们在11例明显无关的患者中发现了10个不同的新移码突变。在两种情况下，检测到额外的错义突变。一个先前描述为致病性种系突变（S2621 C），与相对等位基因上的1-bp插入（4684 insA）相关，未与家族中的FAP表型分离，因此被认为是非致病性的。另一个（Z1625 H）位于一个1bp缺失（4897 delC）前2个密码子处。这两种突变一起从FAP父亲传给了他受影响的儿子。这10个新的截短突变的FAP表型在临床上被记录在它们的激酶中。在表型中观察到重要的变异性。有趣的是，我们注意到在两个不相关的家族中位于5'减毒APC表型区域边界的突变（487 insT）导致经典息肉病。一个明确的基因型-表型相关性可以得出只有两个例子。在一个家系中，4684 insA突变导致与早期遗传性骨瘤相关的轻度息肉病，在携带双突变（Z1625 H +4897 delC）的家系中，表型明显为3′减弱型。我们的数据说明了广泛的遗传和表型异质性，这种情况之间和家庭内，建立相关性复杂，在这种疾病的任何预测困难，虽然在某些特定情况下，针对突变位点可能是有帮助的。
Abstract Among 23 germline mutations identified in the APC screening of 45 familial adenomatous polyposis (FAP) patients, we have found 10 different novel frameshift mutations in 11 apparently unrelated patients. In two cases, an additional missense mutation was detected. One previously described as a causative germline mutation (S2621C), associated with a 1-bp insertion (4684insA) on the opposite allele, did not segregate with the FAP phenotype in the family and was therefore considered as being non-pathogenic. The other (Z1625H) was located 2 codons before a 1-bp deletion (4897delC). Both mutations were transmitted together from an FAP father to his affected son. The FAP phenotype of these 10 novel truncating mutations was clinically documented within their kindreds. Important variability was observed in the phenotype. Interestingly, we noted that a mutation (487insT) localized at the boundary of the 5’ attenuated APC phenotype region in two unrelated families resulted in classical polyposis. A clear-cut genotype-phenotype correlation could be drawn in only two instances. In one family, a 4684insA mutation led to a mild polyposis associated with early inherited osteomas and, in the family bearing the double mutation (Z1625H+4897delC), the phenotype was obviously a 3′ attenuated type. Our data illustrate the wide genetic and phenotypic heterogeneity of this condition between and within the families, making the establishment of correlations complex and any prediction in this disease difficult, although targeting the mutation site may be helpful in some specific cases.
野生型和突变型 APC 基因产物之间的关联。
影响因子：
11.2
作者：
Su,LK;Johnson,KA;Smith,KJ;Hill,DE;Vogelstein,B;Kinzler,KW
通讯作者：
Kinzler,KW
影响因子：
56.9
作者：
KINZLER, KW;NILBERT, MC;NAKAMURA, Y
通讯作者：
NAKAMURA, Y