Ljung R, Kling S, Sjörin E, Nilsson I M
Department of Paediatrics, University of Lund, Malmö General Hospital, Sweden.
Acta Paediatr Scand. 1991 Mar;80(3):343-8. doi: 10.1111/j.1651-2227.1991.tb11860.x.
The aim of this study was to ascertain how many of the sporadic cases of severe Haemophilia A in Sweden are due to recent mutation, and establish its origin. DNA analysis was performed in 18 randomly selected families with a sporadic case of severe haemophilia A. Restriction fragment length polymorphism (RFLP) patterns were investigated, two intragenic (Bc1 I, Xba I/Kpn I) and two extragenic (DX 13, St 14) RFLP being used. In 10/18 families a haemophilia-linked gene was found to have derived from the healthy maternal grandfather; on the basis of clotting and immunological assay results, the odds were high (greater than 104:1) for maternal carriership in four of these 10 cases, and for maternal non-carriership in two, four being indeterminate. In 4/18 families a haemophilia-linked gene derived from the healthy maternal grandmother; according to clotting and immunological assay results, in two cases the odds were high for maternal non-carriership. In the remaining 4/18 families no conclusions could be drawn from the RFLP pattern as to the origin of mutation. We conclude that at least 55% of the sporadic cases of severe hemophilia A in Sweden are due to a recent mutation within the last two generations.
本研究的目的是确定瑞典散发性重度甲型血友病病例中有多少是由近期突变引起的，并确定其起源。对18个随机选择的患有散发性重度甲型血友病的家庭进行了DNA分析。研究了限制性片段长度多态性（RFLP）模式，使用了两种基因内（Bc1 I、Xba I/Kpn I）和两种基因外（DX 13、St 14）RFLP。在10/18的家庭中，发现与血友病相关的基因来自健康的外祖父；根据凝血和免疫分析结果，在这10例中的4例中，母亲为携带者的可能性很高（大于104:1），2例中母亲为非携带者，4例不确定。在4/18的家庭中，与血友病相关的基因来自健康的外祖母；根据凝血和免疫分析结果，在2例中母亲为非携带者的可能性很高。在其余4/18的家庭中，从RFLP模式无法得出关于突变起源的结论。我们得出结论，瑞典至少55%的散发性重度甲型血友病病例是由过去两代内的近期突变引起的。
