Objective: To apply a Hidden Markov Model to test Hemophilia B in a fetus by maternal plasma sequencing only employing proband and maternal haplotypes.
Case report: A family at risk for Hemophilia B was recruited in this study. We performed genetic diagnosis on the proband using our targeted capture system (containing F9 gene coding region, highly heterozygous SNPs and a 13-kb chromosome Y specific region), and revealed a causative F9 gene mutation (c.190T>C, p.Cys64Arg). Maternal plasma cell-free DNA obtained at 8 weeks of gestation was targeted-captured and sequenced using the customized system. The fetus inherited the F9 (c.190T>C, p.Cys64Arg) mutation according to the Hidden Markov Model. The mother continued the pregnancy.
Conclusions: This study is the first report of a haplotype-based approach in NIPD of Hemophilia B. With further evaluation, this method might be useful for NIPD of Hemophilia B and for other X-linked single-gene disorders.
Keywords: Hemophilia B; Massively parallel sequencing; Noninvasive prenatal diagnosis; Single-gene disorders; Target-gene capture.
Copyright © 2017. Published by Elsevier B.V.