Lynch H T, Lemon S, Smyrk T, Franklin B, Karr B, Lynch J, Slominski-Caster S, Murphy P, Connolly C
Department of Preventive Medicine, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
Am J Gastroenterol. 1996 Dec;91(12):2489-93.
Molecular genetic advances have increased the demand for DNA testing. We describe DNA based genetic counseling in a hereditary nonpolyposis colorectal cancer (HNPCC) family.
This extended HNPCC family was found to harbor the MSH2 germline mutation. Family history, medical, and pathology documents enabled us to secure a high degree of verification that the kindred qualified as HNPCC. DNA testing revealed the MSH2 germline mutation that was verified independently in two laboratories. Genetic counseling was provided before DNA testing and disclosure of MSH2 findings.
Genetic counseling revealed a variety of findings characterized by emotional stress in MSH2 germline mutation carriers. Concerns centered around reproductive issues, potential transmission of the deleterious gene to their progeny, and discrimination by insurance carriers and employers. More than one-half of the patients found to harbor the MSH2 mutation considered the option of prophylactic subtotal colectomy.
DNA testing should be restricted to well-verified candidate families in which genetic counseling should be mandatory. HNPCC family members sought genetic risk assessment for their own health and that of their children. Contrasting emotional responses took place when told of their gene testing status and this required a sensitive empathetic listening ear. Patients have many concerns about their lifetime cancer destiny when told that they harbor the culprit MSH2 germline mutation.
分子遗传学的进展增加了对DNA检测的需求。我们描述了一个遗传性非息肉病性结直肠癌（HNPCC）家族中基于DNA的遗传咨询情况。
这个大家庭被发现携带MSH2种系突变。家族病史、医疗和病理文件使我们能够高度确认该家族符合HNPCC的标准。DNA检测揭示了MSH2种系突变，该突变在两个实验室得到了独立验证。在进行DNA检测和披露MSH2检测结果之前，提供了遗传咨询。
遗传咨询揭示了多种结果，其特点是MSH2种系突变携带者存在情绪压力。关注点集中在生殖问题、有害基因向后代的潜在传递以及保险公司和雇主的歧视。超过一半被发现携带MSH2突变的患者考虑了预防性次全结肠切除术的选择。
DNA检测应限于经过充分验证的候选家族，在这些家族中遗传咨询应是强制性的。HNPCC家族成员为自己和孩子的健康寻求遗传风险评估。当被告知他们的基因检测状态时，出现了不同的情绪反应，这需要一个敏感且有同理心的倾听者。当患者被告知他们携带致病的MSH2种系突变时，他们对自己一生的癌症命运有许多担忧。
