Walpole I R, Kool D A, Edkins T, Creegan R, Levitt S, Francis S T, Goldblatt J
Genetic Services of Western Australia, King Edward Memorial Hospital for Women, Perth.
Med J Aust. 1995 May 1;162(9):464-7. doi: 10.5694/j.1326-5377.1995.tb140006.x.
To assess the provision of accurate pre-symptomatic genetic testing with DNA analysis and appropriate counselling for individuals and families known to be at high risk of developing familial adenomatous polyposis coli (FAP).
Thirty-one families with clinically and pathologically documented FAP were ascertained from the Western Australian Polyposis Registry. DNA was collected from over 200 individuals in these families to establish their genetic risk status for FAP, either by direct mutation analysis, or by linkage analysis. Individuals undergoing DNA testing were given intensive psychosocial support and counselling.
In 19 families DNA-based counselling could not be offered because either the adenomatous polyposis coli (APC) gene mutation could not be detected or there were insufficient family members for linkage analysis. Gene testing yielded mutations of the APC gene in 87 individuals from 12 families; by gene tracking (or linkage analysis) in three families and by mutation analysis in the remaining nine (four of which had only one affected individual). DNA results conformed with a definite clinicopathological diagnosis in 27 FAP patients and, of the remaining 60 high-risk subjects tested, 14 had inherited the mutated APC gene.
DNA analysis allowed accurate genetic counselling for 12 of 31 families affected by FAP, thus improving the medical and personal management in asymptomatic people who would otherwise be subjected to the uncertainty of long term surveillance and repeated colonic examinations. In future a superior biomolecular approach to gene mutation analysis, such as the protein truncation test, will facilitate management for most FAP individuals and families.
对已知患家族性腺瘤性息肉病（FAP）风险高的个人和家庭，评估通过DNA分析提供准确的症状前基因检测以及适当的咨询服务。
从西澳大利亚息肉病登记处确定了31个临床和病理记录确诊为FAP的家庭。从这些家庭的200多名个体中收集DNA，通过直接突变分析或连锁分析确定他们患FAP的遗传风险状态。接受DNA检测的个体获得了强化的心理社会支持和咨询服务。
在19个家庭中，由于无法检测到腺瘤性息肉病（APC）基因突变或家庭成员不足无法进行连锁分析，无法提供基于DNA的咨询服务。基因检测在12个家庭的87名个体中发现了APC基因突变；其中3个家庭通过基因追踪（或连锁分析），其余9个家庭通过突变分析（其中4个家庭只有1名受影响个体）。DNA检测结果与27例FAP患者明确的临床病理诊断相符，在其余60名接受检测的高危受试者中，有14人遗传了突变的APC基因。
DNA分析使31个受FAP影响的家庭中的12个家庭能够获得准确的遗传咨询，从而改善了无症状人群的医疗和个人管理，否则这些人将面临长期监测和反复结肠检查的不确定性。未来，一种更优的基因突变分析生物分子方法，如蛋白质截短试验，将有助于大多数FAP个体和家庭的管理。
