Genetic counselling in haemophilia by discriminant analysis 1975-1980*
Genetic counselling in haemophilia by discriminant analysis 1975-1980*
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1975-1980 年通过判别分析对血友病进行遗传咨询*
DOI：
10.1136/jmg.19.1.26
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发表时间：
1982
影响因子：
4
通讯作者：
J. B. Graham
中科院分区：
文献类型：
--
作者：
E. Barrow;Connie H. Miller;H. Reisner;J. B. Graham
1975年1月至1980年1月间，我们对214名可能的或强制的A型血友病携带者进行了咨询，试图为他们提供所需的咨询，并确定分配杂合基因型的概率方法（携带者检测）的效用。我们发现分配的方法是快速和容易使用的，和单一的输出（最终概率有利于运载P(C)），大多数辅导员理解。在80%的女性中，最终获得的概率不是很高就是很低，这使得我们在五分之四的情况下给出了明确的建议。最终概率也可用于将孟德尔期望与三个女性亚群（18名散发性血友病患者的母亲，78名姐妹和62名更远的亲属）中的观察结果联系起来，而强制性携带者的6/36（17%）的异常似然比提供了由于游离化而导致的假阴性诊断率的估计。强制性携带者的VIII:C和VIII: Ag水平没有明显的年龄影响，从父亲那里获得基因的强制性携带者的VIII:C水平与从母亲那里获得基因的强制性携带者的VIII:C水平没有差异。血友病患者的姐妹和远亲的高概率与低概率的比值符合遗传预期，而散发性血友病患者的母亲的比值表明，她们对携带血友病的期望大于80%。214名咨询师中有20人（9%）在第一次就诊时怀孕，低P(C)s（0 -0 . 33）的13人足月分娩，并分娩了11名非血友病患儿。P(C)值在0.50 ~ 0.00之间的4只要求羊膜穿刺术，1只雄性流产。三名强制性携带者也要求进行羊膜穿刺术，导致另一名男性流产。7名妇女在怀孕前接受评估，发现P(C)值高，在怀孕后返回。发现的7名男性中有6名要求进行羊膜穿刺术（1名两次）和胎儿镜检查，其中1名男性在进行胎儿镜检查之前已经流产。在接受胎儿镜检查的6名男性中，3名正常男性足月，1名正常男性早产，1名血友病男性和1名正常男性没有在胎儿镜检查中存活。
Between January 1975 and January 1980 we counselled 214 possible or obligatory carriers of haemophilia A in an attempt to provide the counsel they needed and to determine the utility of a probabilistic method of assigning the heterozygous genotype (carrier detection). We found the method of assignment to be quick and easy to use, and the single output (the final probability favouring carriership P(C)) to be understood by most counsellees. The final probabilities obtained were either very high or very low in 80% of the women, which allowed us to give clear counsel in four instances in five. The final probabilities could also be used to relate Mendelian expectation to observation within each of three subsets of women (18 mothers of sporadic haemophiliacs, 78 sisters, and 62 more distant relatives), while the aberrant likelihood ratios of 6/36 (17%) of the obligatory carriers provided an estimate of the false negative diagnostic rate owing to lyonisation. There was no significant age effect on VIII:C or VIIIR:Ag levels of obligatory carriers, and the VIII:C levels of the obligatory carriers who had received the gene from their fathers did not differ from those of the obligatory carriers who had received the gene from their mothers. The ratios of high:low probabilities among the sisters and distant relatives of haemophiliacs conformed to genetic expectation, while the ratio among mothers of sporadic haemophiliacs suggested that their expectations of carriership were greater than 80%. Twenty of the 214 counsellees (9%) were pregnant on the first visit, and 13 of those with low P(C)s (0·0-0·33) went to term and delivered 11 non-haemophilic children. Four with P(C)s between 0·50 and 1·00 requested amniocenteses, and one male was aborted. Three who were obligatory carriers also requested amniocentesis which led to the abortion of a second male. Seven women who were assessed before pregnancy and found to have high P(C)s returned after becoming pregnant. All requested amniocentesis (one twice) and fetoscopy was requested for six of the seven males discovered, one male having been aborted before fetoscopy became available. Of the six males who were fetoscoped, three normal males reached term, one normal male was born prematurely, and one haemophilic male and one normal male did not survive fetoscopy.