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

https://doi.org/10.1016/j.tjog.2017.08.020Get rights and content
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Abstract

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

Massively parallel sequencing
Hemophilia B
Noninvasive prenatal diagnosis
Single-gene disorders
Target-gene capture

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1

Equal contribution.