Moisio A-L, Järvinen H, Peltomäki P
Department of Medical Genetics, Biomedicum Helsinki, PO Box 63, FIN-00014 University of Helsinki, Finland.
Gut. 2002 Jun;50(6):845-50. doi: 10.1136/gut.50.6.845.
Familial adenomatous polyposis (FAP) is a rare autosomal dominantly inherited disease predisposing to colon cancer and caused by germline mutations in the APC (adenomatous polyposis coli) gene.
We conducted a population based study to evaluate the prevalence and clinical implications of APC mutations among Finnish FAP kindreds. A possible founder effect in parallel with previous observations in hereditary non-polyposis colon cancer (HNPCC) was addressed.
Affected individuals from 65 kindreds were included.
The APC gene was screened for mutations using the protein truncation test and heteroduplex analysis. Haplotype analysis was performed with four flanking microsatellite markers. Families that failed to show any mutations were scrutinised with Southern blot hybridisation and allelic expression analysis.
Thirty eight different germline mutations in APC were identified in 47 kindreds (72%). The majority of these mutations were novel and unique to each family. Although sharing the classical polyposis phenotype, families without detectable APC mutations differed from mutation positive families in the following respects: firstly, mean age at polyposis diagnosis was higher (38.6 years (48 individuals) v 30.0 years (140 individuals); p=0.001); and secondly, the proportion of kindreds lacking extracolonic disease was higher (6/18 v. 5/47; p=0.04).
Our results may pave the way for predictive testing in mutation positive families and should stimulate further molecular studies in mutation negative families. No founder effect was observed, which is in contrast with HNPCC in the same population.
家族性腺瘤性息肉病（FAP）是一种罕见的常染色体显性遗传病，易患结肠癌，由APC（腺瘤性息肉病 coli）基因的种系突变引起。
我们进行了一项基于人群的研究，以评估芬兰FAP家族中APC突变的患病率及其临床意义。探讨了与遗传性非息肉病性结肠癌（HNPCC）先前观察结果类似的可能的奠基者效应。
纳入了来自65个家族的受影响个体。
使用蛋白质截短试验和异源双链分析筛选APC基因的突变。用四个侧翼微卫星标记进行单倍型分析。对未显示任何突变的家族进行Southern印迹杂交和等位基因表达分析。
在47个家族（72%）中鉴定出38种不同的APC种系突变。这些突变大多数是新的，且每个家族都不同。尽管具有典型的息肉病表型，但未检测到APC突变的家族在以下方面与突变阳性家族不同：首先，息肉病诊断时的平均年龄较高（38.6岁（48人）对30.0岁（140人）；p = 0.001）；其次，缺乏结肠外疾病的家族比例较高（6/18对5/47；p = 0.04）。
我们的结果可能为突变阳性家族的预测性检测铺平道路，并应促进对突变阴性家族的进一步分子研究。未观察到奠基者效应，这与同一人群中的HNPCC相反。
