Tizzano E F, Domènech M, Baiget M
Molecular Genetics Unit, Santa Creu i Sant Pau Hospital, Barcelona, Spain.
Thromb Haemost. 1995 Jan;73(1):6-9.
Inversion involving intron 22 is the commonest type of mutation causing severe hemophilia A (HA). We investigated 15 families with isolated cases and 5 families with two or three brothers as the only affected members with hemophilia A, in order to determine the carrier status of the mothers, the origin of the mutation and the presence of germinal mosaicism. Our results show that all mothers tested were carriers of the inversion. In addition, three families whose unique hemophilic member was not available for analysis, were screened for the inversion. In one of these last families, the mother was diagnosed as a carrier and her sister and her niece as non-carriers. DNA haplotype analysis in 8 families with grandparents available for study demonstrated that the inversion originated almost exclusively in male germ cells. These findings have important relevance for genetic counselling in families with an isolated case or to exclude germinal mosaicism. Inversion analysis should constitute the first step in molecular diagnosis of severe hemophilia A.
涉及内含子22的倒位是导致严重甲型血友病（HA）的最常见突变类型。我们调查了15个仅有单个病例的家庭以及5个有两到三个兄弟为仅有的甲型血友病患者的家庭，以确定母亲的携带者状态、突变起源以及生殖腺嵌合体的存在情况。我们的结果显示，所有接受检测的母亲均为倒位携带者。此外，对三个其唯一的血友病成员无法进行分析的家庭进行了倒位筛查。在这最后三个家庭中的一个，母亲被诊断为携带者，而她的姐妹和侄女被诊断为非携带者。对8个有祖父母可供研究的家庭进行的DNA单倍型分析表明，倒位几乎完全起源于男性生殖细胞。这些发现对于仅有单个病例的家庭进行遗传咨询或排除生殖腺嵌合体具有重要意义。倒位分析应成为严重甲型血友病分子诊断的第一步。
