Noninvasive prenatal diagnosis of hemophilia A by a haplotype-based approach using cell-free fetal DNA. 2020

Chao Chen, and Jun Sun, and Yun Yang, and Lu Jiang, and Fengyu Guo, and Yaping Zhu, and Dan Li, and Renhua Wu, and Rong Lu, and Mei Zhao, and Fang Chen, and Peixiang Ni, and Zhihui He, and Zhiyu Peng
Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Central Avenue 55, Airport Business Park East Building E3, Tianjin 300308, China.

Aim: We aimed to demonstrate noninvasive prenatal diagnosis (NIPD) of hemophilia A (HA) using a haplotype-based approach. Methods: Two families at risk for HA were recruited for this study. First, maternal haplotypes associated with pathogenic variants were constructed using the genotypes of the mothers and probands. Then, fetal haplotypes were deduced using a maternal haplotype-assisted hidden Markov model. Finally, the NIPD results were further confirmed by invasive prenatal diagnosis. Results: Two fetal genotypes were successfully inferred, with one normal fetus and one carrier fetus. The NIPD results were confirmed by invasive prenatal diagnosis, with a 100% consistency rate. Conclusion: Our test has been shown to be accurate and reliable. With further validation in a large patient cohort, this haplotype-based approach could be feasible for the NIPD of HA and other X-linked single-gene disorders.

UI MeSH Term Description Entries
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D005260 Female Females
D006467 Hemophilia A The classic hemophilia resulting from a deficiency of factor VIII. It is an inherited disorder of blood coagulation characterized by a permanent tendency to hemorrhage. Factor VIII Deficiency,Hemophilia,Autosomal Hemophilia A,Classic Hemophilia,Deficiency, Factor VIII,Factor 8 Deficiency, Congenital,Factor VIII Deficiency, Congenital,Haemophilia,Hemophilia A, Congenital,Hemophilia, Classic,As, Autosomal Hemophilia,Autosomal Hemophilia As,Classic Hemophilias,Congenital Hemophilia A,Congenital Hemophilia As,Hemophilia A, Autosomal,Hemophilia As,Hemophilia As, Autosomal,Hemophilia As, Congenital,Hemophilias, Classic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000073888 Cell-Free Nucleic Acids Nucleic acids (DNA or RNA) found circulating in SERUM; PLASMA; or other BODY FLUIDS. Circulating Cell-Free Nucleic Acid,Circulating Nucleic Acid,Cell-Free DNA,Cell-Free Deoxyribonucleic Acid,Cell-Free Nucleic Acid,Cell-Free RNA,Cell-Free Ribonucleic Acid,Circulating Cell-Free Nucleic Acids,Circulating DNA,Circulating Nucleic Acids,Circulating RNA,cfDNA,cfRNA,cirDNA,cirRNA,Acid, Cell-Free Deoxyribonucleic,Acid, Cell-Free Ribonucleic,Acid, Circulating Nucleic,Acids, Circulating Nucleic,Cell Free DNA,Cell Free Deoxyribonucleic Acid,Cell Free Nucleic Acid,Cell Free Nucleic Acids,Cell Free RNA,Cell Free Ribonucleic Acid,Circulating Cell Free Nucleic Acid,Circulating Cell Free Nucleic Acids,DNA, Cell-Free,DNA, Circulating,Deoxyribonucleic Acid, Cell-Free,Nucleic Acid, Cell-Free,Nucleic Acid, Circulating,Nucleic Acids, Cell-Free,Nucleic Acids, Circulating,RNA, Cell-Free,RNA, Circulating,Ribonucleic Acid, Cell-Free
D000081182 Noninvasive Prenatal Testing The analysis of cell-free fetal DNA or the DNA from fetal cells that are biopsied from a pregnant woman’s blood, to screen for genetically-determined traits and genetic abnormalities. Noninvasive Prenatal Diagnosis,Noninvasive Prenatal Screening,Prenatal Cell-Free DNA Screening,Prenatal cfDNA Screening,Prenatal Cell Free DNA Screening,Prenatal Diagnosis, Noninvasive,Prenatal Screening, Noninvasive,Prenatal Testing, Noninvasive,cfDNA Screening, Prenatal

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