Zhang Z P, Blombäck M, Nyman D, Anvret M
Department of Clinical Chemistry, Karolinska Hospital, Stockholm, Sweden.
Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7937-40. doi: 10.1073/pnas.90.17.7937.
Patients with von Willebrand disease in four families in the Aland Islands, including the original family that was described in 1926 by the Finnish physician von Willebrand, were screened for mutations in the Swedish "hot-spot" regions (exons 18, 28, 32, 43, and 45) of the von Willebrand factor gene. One cytosine deletion in exon 18 was detected in each of these families. Linkage analysis and genealogical studies suggest that the deletion present in these four families probably has an origin in common with the mutations in the Swedish patients. Apart from the deletion in exon 18, two close transitions (G-->A at S1263 and C-->T at P1266) in exon 28 on the same chromosome were identified in one individual who married into the original family and in his two children. The transitions could be due to a recombination between the von Willebrand factor gene and its pseudogene.
奥兰群岛四个家族中的血管性血友病患者，包括芬兰医生冯·维勒布兰德于1926年描述的最初那个家族，均接受了血管性血友病因子基因瑞典“热点”区域（外显子18、28、32、43和45）突变筛查。在这些家族的每一个中均检测到外显子18中的一个胞嘧啶缺失。连锁分析和系谱研究表明，这四个家族中存在的缺失可能与瑞典患者的突变有共同起源。除了外显子18中的缺失外，在一个与最初家族通婚的个体及其两个孩子中，在同一条染色体的外显子28中鉴定出两个紧密的转换（S1263处的G→A和P1266处的C→T）。这些转换可能是由于血管性血友病因子基因与其假基因之间的重组所致。
