Noninvasive prenatal diagnosis for Hemophilia A by haplotype-based approach using cell-free fetal DNA in maternal plasma

Objectives This study was used to demonstrate the feasibility of haplotype-based noninvasive prenatal diagnosis for Hemophilia A. Methods Two families affected by Hemophilia A participated in our study. Maternal haplotypes associated with pathogenic mutation was built using targeted region genotypes of mother and the proband. Combined with maternal pathogenic haplotype, a Hidden Markov Model was constructed to deduce fetal haplotype using high-coverage targeted sequencing of maternal plasma. The presence of pathogenic haplotype in male indicated affected fetus, in female indicated carrier. Prenatal diagnosis was confirmed with amniocentesis by long distance PCR. Results The haplotype-based noninvasive prenatal diagnosis was successfully performed in Hemophilia A. One fetus was identified to be normal, another fetus was identified as carrier, and the results were confirmed by amniocentesis . Conclusion Our research demonstrated the feasibility of noninvasive prenatal diagnosis for Hemophilia A by haplotype-based approach.