Meissen G J, Myers R H, Mastromauro C A, Koroshetz W J, Klinger K W, Farrer L A, Watkins P A, Gusella J F, Bird E D, Martin J B
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston.
N Engl J Med. 1988 Mar 3;318(9):535-42. doi: 10.1056/NEJM198803033180903.
The probability of carrying the gene for Huntington's disease can in many cases be estimated in the children of affected persons by identifying a specific DNA marker that is genetically linked to the gene. We studied 47 persons at 50 percent risk of inheriting Huntington's disease who requested a presymptomatic or prenatal genetic-linkage test between September 1986 and January 1988. The participants were given pre-test counseling and psychological and neurologic evaluations. Nineteen persons later voluntarily withdrew from the protocol, including one who would have been excluded anyway, and one person was from a family that was too small to allow testing. Three D4S10 restriction-fragment-length polymorphisms produced by the HindIII, EcoRI, and Bg/I enzymes were used for all tests, and the probability that a subject was a Huntington's disease carrier was calculated. The accuracy of the test was compromised by a 4 percent recombination frequency between D4S10 and the Huntington's disease gene. Fifteen presymptomatic tests and one prenatal test were completed. Four yielded positive results, seven yielded negative results, and five were uninformative; seven persons are awaiting test results. All participants with positive tests experienced intermittent depression, but none required hospitalization, and no suicide threats were reported. Five participants received a diagnosis of Huntington's disease on the basis of the neurologic assessment. We conclude that some persons in the early stages of Huntington's disease may seek presymptomatic testing rather than neurologic evaluations.
在许多情况下，通过识别与亨廷顿舞蹈病基因存在遗传联系的特定DNA标记，可估计患者子女携带该基因的概率。我们对47名有50%遗传亨廷顿舞蹈病风险的人进行了研究，他们在1986年9月至1988年1月期间要求进行症状前或产前基因连锁检测。参与者接受了检测前咨询以及心理和神经学评估。19人后来自愿退出了该方案，其中包括1名无论如何都会被排除的人，还有1人来自一个规模太小无法进行检测的家庭。所有检测均使用由HindIII、EcoRI和Bg/I酶产生的三种D4S10限制性片段长度多态性，并计算了受试者为亨廷顿舞蹈病携带者的概率。由于D4S10与亨廷顿舞蹈病基因之间存在4%的重组频率，检测的准确性受到了影响。完成了15次症状前检测和1次产前检测。4次检测结果为阳性，7次为阴性，5次无信息价值；7人正在等待检测结果。所有检测结果为阳性的参与者都经历了间歇性抑郁，但无人需要住院治疗，也未报告有自杀威胁。5名参与者根据神经学评估被诊断为亨廷顿舞蹈病。我们得出结论，一些处于亨廷顿舞蹈病早期阶段的人可能会寻求症状前检测而非神经学评估。
