Caspari R, Friedl W, Böker T, Augustin A, Mandl M, Jaeger K, Gallkowski K, Propping P
Institut für Humangenetik, Universität, Bonn.
Z Gastroenterol. 1993 Nov;31(11):646-52.
Familial adenomatous polyposis (FAP) is an autosomal-dominant precancerous condition characterized by the appearance of hundreds to thousands of colorectal polyps. The responsible gene (APC) has been mapped and identified. The cancer prevention policy for persons at risk (children and sibs of FAP patients) implies an early diagnosis of the disease. A presymptomatic diagnosis allows to limit the regular rectosigmoidoscopic examination to those persons having inherited the disease gene. Presymptomatic diagnosis can be achieved by molecular genetic methods (direct and indirect genotype analysis) and by funduscopic examination of retinal pigment anomalies that are characteristic for FAP. The aim of this study was to examine the power of the molecular genetic and ophthalmologic methods for presymptomatic diagnosis in FAP. For this purpose 60 FAP families with 171 persons at risk were examined. By direct mutation analysis a presymptomatic diagnosis was achieved in 32% of the persons at risk; indirect genotype analysis was possible in 88% of the families in which more than one FAP patient was available. The ophthalmologic examination allowed a presymptomatic conclusion in 79% of the persons at risk. In no case there was a discrepancy in the results between the methods applied. The ophthalmologic presymptomatic test is useful especially in families where the index patients has a new mutation in the APC gene that has not been identified.
家族性腺瘤性息肉病（FAP）是一种常染色体显性癌前疾病，其特征是出现数百至数千个结肠息肉。相关基因（APC）已被定位和识别。针对高危人群（FAP患者的子女和兄弟姐妹）的癌症预防策略意味着要对该疾病进行早期诊断。症状前诊断可将常规乙状结肠镜检查局限于那些继承了疾病基因的人。症状前诊断可通过分子遗传学方法（直接和间接基因型分析）以及对FAP特有的视网膜色素异常进行眼底镜检查来实现。本研究的目的是检验分子遗传学和眼科方法对FAP症状前诊断的效能。为此，对60个FAP家族中的171名高危个体进行了检查。通过直接突变分析，32%的高危个体实现了症状前诊断；在有不止一名FAP患者的88%的家族中可以进行间接基因型分析。眼科检查使79%的高危个体得出了症状前结论。所应用的方法之间在结果上从未出现过差异。眼科症状前检测尤其适用于索引患者在APC基因中有未被识别的新突变的家族。
