Grobbelaar J J, Ziskind A, de Jong G, Oosthuizen C J, Kotze M J
Department of Human Genetics, Faculty of Medicine, University of Stellenbosch, Tygerberg, South Africa.
J Med Genet. 1996 May;33(5):384-6. doi: 10.1136/jmg.33.5.384.
A novel mutation at codon 441 in exon 10 of the adenomatous polyposis coli (APC) gene was identified in a South African family of mixed ancestry, using a convenient, non-radioactive, heteroduplex-SSCP screening assay. This single thymidine deletion after nucleotide position 1322 creates a frameshift resulting in a downstream stop codon at amino acid residue 453 of the APC gene. Genotypes of nine family members were subsequently correlated with the presence or absence of congenital hypertrophy of the retinal pigment epithelium (CHRPE), since expression of this common extracolonic manifestation of FAP is largely determined by the length of the truncated protein. CHRPE was absent in the five unaffected family members analysed, while four mutation positive subjects showed these ophthalmic lesions. Correlation between the molecular analysis and ophthalmic examinations, performed without knowledge of clinical and genetic status respectively, provided additional evidence in favour of the view that the range of phenotypic expression in FAP may result from different allelic manifestations of APC mutations.
采用一种简便、非放射性的异源双链 - SSCP 筛查方法，在一个具有混合血统的南非家族中，鉴定出腺瘤性息肉病 coli（APC）基因第 10 外显子第 441 密码子处的一种新型突变。核苷酸位置 1322 后的单个胸腺嘧啶缺失导致移码，从而在 APC 基因的氨基酸残基 453 处产生一个下游终止密码子。随后，由于 FAP 这种常见的结肠外表现的表达很大程度上由截短蛋白的长度决定，因此对九名家族成员的基因型与视网膜色素上皮先天性肥大（CHRPE）的有无进行了关联分析。在分析的五名未受影响的家族成员中未发现 CHRPE，而四名突变阳性受试者出现了这些眼部病变。分别在不了解临床和遗传状况的情况下进行的分子分析与眼科检查之间的相关性，为以下观点提供了更多证据，即 FAP 中表型表达的范围可能源自 APC 突变的不同等位基因表现形式。
