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

• Published in: Taiwanese journal of obstetrics & gynecology 2017-10, Vol.56 (5), p.686-690
• Main Authors: Hu, Ping, Qiao, Fengchang, Yuan, Yuan, Sun, Ruihong, Wang, Yan, Meng, Lulu, Lin, Ying, Li, Hang, Wang, Yaoshen, Han, Rui, Liang, Dong, Ma, Dingyuan, Jiang, Tao, Jiang, Hui, Xu, Zhengfeng
• Format: Article
• Language: English
• Subjects: Hemophilia B; Massively parallel sequencing; Noninvasive prenatal diagnosis; Single-gene disorders; Target-gene capture
• ISSN: 1028-4559
• 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.