Prenatal diagnosis for fetus with hemophilia A

Abstract

To study the prenatal genetic diagnostic methods for hemophilia A fetus. From 2002 to 2006, 19 hemophilia A families were diagnosed either by long distance-polymerase chain reaction (LD-PCR) for factor VIII intron 22 inversion or by the DNA polymorphism genetic linkage analysis of factor VIII in the Beijing Chaoyang Hospital. (1) Totally 19 women, with 22 pregnancies received the prenatal diagnosis of fetal hemophilia A. The average week at diagnosis was 23 (17-34 ) weeks. All the direct fetal blood sampling (DFBS) were successful. There was no fetal-loss caused by the procedures. (2) Of the 19 hemophilia A families, 14 appeared to be factor VIII intron 22 inversion, in which 16 prenatal diagnoses were done, 10 fetuses were diagnosed as genetical hemophilia A patients, and 6 fetuses were normal. (3) Using combined polymorphism genetic linkage analysis 6 prenatal diagnoses were done, including one woman's two pregnancies, in which both her fetuses were diagnosed as genetical hemophilia A patients. (4) Factor VIII levels of 16 fetuses were measured, and 6 fetuses were unmeasured either because the pregnancy weeks were lower than 20 weeks or the parents refused. Factor VIII level ranged from 0 to 198%. There were 11 fetuses whose factor VIII levels were lower than 10%. Ten of them were diagnosed to be genetical hemophilia A patients, and in only one boy the factor VIII level was 2%, but the genetic diagnosis was normal and for one year's follow up he was doing normal. LD-PCR combined with polymorphism genetic linkage analysis enables a quick and correct detection of hemophilia A carrier. For a carrier pregnancy, prenatal diagnosis could be done for the male fetus. Factor VIII deficiency of the fetus could help make the diagnosis but the final diagnosis should be based on genetic evidence.