血友病A携带者检测与产前诊断

目的 建立简便、快速的血友病A携带者检测与产前诊断体系。方法 用PCR方法直接检测FⅧ内含子22倒位或对FⅧ基因内的BclⅠ位点、内含子13和22中STR和FⅧ基因外的DXS52（ST14）位点的多态性进行遗传连锁分析。结果 应用内含子22例位的直接诊断率为47．6％；Bcl Ⅰ位点的可诊断率为27．8％；内含子13和22中STR的可诊断率分别为28．6％及29．4％；DCS52的可诊断率为81．3％；综合应用直接诊断和间接遗传连锁分析，对21个家系进行检测，可诊断率为94．7％。结论 血友病A的携带者检测与产前诊断可先进行内含子22倒位的检测，若结果为阳性即可作出诊断；若内含子22例位的检测结果为阴性，则可利用FⅧ基因内、外的多个位点多态性结果进行遗传连锁分析，以作出最终的诊断。

Carrier detection and prenatal diagnosis for hemophilia A

OBJECTIVE: To establish a simple, rapid carrier detection and prenatal diagnosis system for hemophilia A. METHODS: Intron 22 inversion in FVIII gene was directly examined by long distance polymerase chain reaction. Polymorphism of factor VIII intragenic RFLP of Bcl I, STR within intron 13 and 22, and extragenic DXS 52 (St 14) VNTR loci by hereditary linkage analysis were assayed. RESULTS: The diagnostic rates of these loci were 47.6% (intron 22 inversion), 27.8% (Bcl I), 28.6% and 29.4% (STR within intron 13 and 22), and 81.3% (DXS52), respectively. The overall diagnostic rate in 21 families was 94.7%. CONCLUSIONS: The diagnosis in hemophilia A patients or carriers can be made if intron 22 inversion is present. The intragenic and extragenic loci hereditary linkage analysis could be used to establish the diagnosis in intron 22 inversion negative patients.