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

• Main Authors: Ping Hu, Fengchang Qiao, Yuan Yuan, Ruihong Sun, Yan Wang, Lulu Meng, Ying Lin, Hang Li, Yaoshen Wang, Rui Han, Dong Liang, Dingyuan Ma, Tao Jiang, Hui Jiang, Zhengfeng Xu
• Format: Article
• Language: English
• Published: Elsevier 2017-10-01
• Series: Taiwanese Journal of Obstetrics & Gynecology
• Subjects: Massively parallel sequencing; Hemophilia B; Noninvasive prenatal diagnosis; Single-gene disorders; Target-gene capture
• Online Access: http://www.sciencedirect.com/science/article/pii/S1028455917302097

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.