Noninvasive prenatal diagnosis for X-linked disease by maternal plasma sequencing in a family of Hemophilia B

Taiwan J Obstet Gynecol. 2017 Oct;56(5):686-690. doi: 10.1016/j.tjog.2017.08.020.


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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Female
  • Genetic Testing / methods*
  • Haplotypes
  • Hemophilia B / diagnosis*
  • Hemophilia B / genetics
  • Heterozygote
  • Humans
  • Male
  • Maternal Serum Screening Tests / methods*
  • Pedigree*
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Sequence Analysis, DNA / methods*