Abstract of BGI prenatal test
Aim: We aimed to demonstrate noninvasive prenatal diagnosis (NIPD) of hemophilia A (HA) using a haplotype-based approach. Methods: Two families at risk for HA were recruited for this study. First, maternal haplotypes associated with pathogenic variants were constructed using the genotypes of the mothers and probands. Then, fetal haplotypes were deduced using a maternal haplotype-assisted hidden Markov model. Finally, the NIPD results were further confirmed by invasive prenatal diagnosis. Results: Two fetal genotypes were successfully inferred, with one normal fetus and one carrier fetus. The NIPD results were confirmed by invasive prenatal diagnosis, with a 100% consistency rate. Conclusion: Our test has been shown to be accurate and reliable. With further validation in a large patient cohort, this haplotype-based approach could be feasible for the NIPD of HA and other X-linked single-gene disorders.
SUMMARY POINTS
We propose a haplotype-based noninvasive prenatal diagnosis approach for hemophilia A using a small target region. The genomic DNA of the parents and proband and cell-free DNA of maternal plasma are analyzed by targeted sequencing and maternal pathogenic haplotypes deduced using the genotypes of mother and proband. Then, fetal haplotypes were inferred using a hidden Markov model and Viterbi algorithm.
factor VIIIhaplotypehemophilia Anoninvasive prenatal diagnosistargeted sequencing
Hemophilia A (HA) is an X-linked recessive bleeding disorder affecting approximately 1/5000 male live births [1]. HA is caused by a pathogenic variant in the F8 gene, resulting in a qualitative or quantitative deficiency in factor VIII (FVIII). More than 2000 sequence variants in F8 have been collected in the HA databases [2]. The F8 intron 22 inversion (Inv22) is found in approximately half the patients with severe HA [3]. Without prophylactic treatment, patients with severe HA suffer from spontaneous or traumatic bleeding in several organs. Intracranial hemorrhage can occur after even mil |
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