Tassicker R J, Marshall P K, Liebeck T A, Keville M A, Singaram B M, Richards F H
Genetic Health Services Victoria, Royal Children's Hospital, Parkville, Victoria, Australia.
Clin Genet. 2006 Dec;70(6):480-9. doi: 10.1111/j.1399-0004.2006.00701.x.
This study summarizes 10-years' experience of predictive and pre-natal testing and pre-implantation genetic diagnosis (PGD) for Huntington disease (HD) in Australia. Results are presented from 2036 direct mutation predictive tests conducted between January 1994 and December 2003. Thirty-eight per cent of results (776/2036) were positive, 56% (1140/2036) were negative, and 6% (120/2036)) were in the mutable normal (27-35 CAG repeats) or in the reduced penetrance (36-39 CAG repeats) ranges. Ninety-four per cent (1908/2036) and 6% (128/2036) of those tested had prior genetic risks of 50% and 25%, respectively. Twenty-seven per cent (34/128) of those at 25% risk had their genetic status changed to positive, thus revealing the positive status of their at-risk parent. During this period, 63 pre-natal tests were also conducted, and 13 children were born following PGD for HD. Social workers specializing in predictive testing counselling over this 10-year period across Australia identified and summarized particularly challenging counselling issues. These included the interpretation of mutable normal and reduced penetrance range test results, potential conflicts of interest between family members regarding testing decisions, unanticipated consequences of both predictive and pre-natal testing decisions, the importance of following protocols for predictive testing to facilitate long-term adjustment to results, and the potential for genetic discrimination. The identified issues highlight the importance of the protocols for predictive testing and indicate that extension of the international guidelines published in 1994 may be timely.
本研究总结了澳大利亚在亨廷顿舞蹈症（HD）预测性检测、产前检测及植入前基因诊断（PGD）方面的十年经验。文中展示了1994年1月至2003年12月期间进行的2036次直接突变预测性检测结果。38%（776/2036）的检测结果为阳性，56%（1140/2036）为阴性，6%（120/2036）处于可变正常（27 - 35个CAG重复序列）或低外显率（36 - 39个CAG重复序列）范围。接受检测者中，94%（1908/2036）和6%（128/2036）的人分别有50%和25%的先前遗传风险。有25%风险的人群中，27%（34/128）的遗传状态转变为阳性，从而揭示出其高危父母的阳性状态。在此期间，还进行了63次产前检测，13名儿童通过HD的PGD出生。在这十年间，澳大利亚专门从事预测性检测咨询的社会工作者识别并总结了特别具有挑战性的咨询问题。这些问题包括可变正常和低外显率范围检测结果的解读、家庭成员在检测决策上潜在的利益冲突、预测性检测和产前检测决策的意外后果、遵循预测性检测方案以促进对检测结果的长期适应的重要性以及基因歧视的可能性。所识别出的问题凸显了预测性检测方案的重要性，并表明可能需要及时扩展1994年发布的国际指南。
