Friedl W, Meuschel S, Caspari R, Lamberti C, Krieger S, Sengteller M, Propping P
Institut für Humangenetik der Universität Bonn, Germany.
Hum Genet. 1996 May;97(5):579-84. doi: 10.1007/BF02281864.
The identification of germline mutations in a large number of clinically well-characterised patients with familial adenomatous polyposis (FAP) has allowed the unravelling of several genotype-phenotype relationships that can now be interpreted in the light of the structure and functional domains of the adenomatous polyposis coli (APC) protein. An attenuated phenotype has been found to be associated with mutations at the 5' end of the gene, while a severe clinical expression was found in patients with the most common mutation at codon 1309. So far, only few mutations in the 3' half of the gene have been published. We report on two families with a rather mild phenotype due to a frameshift mutation at codon 1597. These families may represent a clue for defining a 5' border for the occurrence of a second region of attenuated FAP that is localised in the 3' part of the APC gene. We propose a model to explain the relationship between the severity of the disease and the size of the mutant APC protein.
在大量临床特征明确的家族性腺瘤性息肉病（FAP）患者中对种系突变进行鉴定，有助于揭示几种基因型与表型的关系，现在可根据腺瘤性息肉病大肠杆菌（APC）蛋白的结构和功能结构域对这些关系进行解读。已发现减弱的表型与基因5'端的突变相关，而在密码子1309处发生最常见突变的患者中则出现严重的临床表型。到目前为止，仅发表了该基因3'半部分的少数突变。我们报告了两个家族，由于密码子1597处的移码突变，其表型相当轻微。这些家族可能为确定位于APC基因3'部分的FAP减弱的第二个区域发生的5'边界提供线索。我们提出一个模型来解释疾病严重程度与突变APC蛋白大小之间的关系。
