Koorey D J, McCaughan G W, Trent R J, Gallagher N D
A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia.
Hum Mutat. 1994;3(1):12-8. doi: 10.1002/humu.1380030103.
The familial adenomatous polyposis gene, APC, has recently been identified. Detection of APC mutations will facilitate genetic screening in family members at risk for this disease. The length of APC makes it impractical to examine the entire coding sequence in each new family encountered. Identification of mutation cluster regions within the gene has therefore become a priority. Initial reports suggested that exon eight might contain a disproportionate number of mutations. This study describes direct sequencing of exon eight in 21 unrelated Australians with familial adenomatous polyposis. Mutations were detected in three of the 21 subjects (14%). Two were previously described point mutations changing an arginine to a stop codon. The third was a novel two base-pair deletion producing a frameshift and downstream stop codon. All three mutations segregated with the disease gene in their respective families. Three at risk children from two of these families were studied and shown not to have inherited the disease producing mutation. These results confirm that exon eight is a frequent site of mutation in familial adenomatous polyposis and should be examined routinely in families requesting genetic screening.
家族性腺瘤性息肉病基因APC最近已被鉴定出来。检测APC突变将有助于对有患此病风险的家庭成员进行基因筛查。由于APC基因长度较长，对每个新遇到的家族检测其整个编码序列并不实际。因此，确定该基因内的突变簇区域已成为当务之急。初步报告表明，第8外显子可能含有不成比例数量的突变。本研究描述了对21名患有家族性腺瘤性息肉病的澳大利亚非亲属个体的第8外显子进行直接测序。在21名受试者中有3名检测到突变（14%）。其中两个是先前描述的将精氨酸变为终止密码子的点突变。第三个是一个新的两个碱基对的缺失，导致移码和下游终止密码子。所有这三个突变在各自家族中均与疾病基因共分离。对其中两个家族的三名有患病风险的儿童进行了研究，结果显示他们没有遗传到导致疾病的突变。这些结果证实，第8外显子是家族性腺瘤性息肉病中常见的突变位点，对于要求进行基因筛查的家族应常规检测该外显子。
