Noninvasive prenatal diagnosis for Duchenne muscular dystrophy based on the direct haplotype phasing

作者：Min Chen, Chao Chen, Xiaoyan Huang, Junwei Sun, Lu Jiang, Yingting Li, Yaping Zhu, Chang-Geng Tian, Yufan Li, Zhe Lu, Yaoshen Wang, Fanwei Zeng, Yun Yang, Xiwei Song, Zhiyu Peng, Chenghong Yin, Dunjin Chen · 发表于：Prenatal Diagnosis · 年份：2020 · DOI：10.1002/pd.5641 · 被引用次数：29 · 研究领域：Muscle Physiology and Disorders、Neurogenetic and Muscular Disorders Research、Prenatal Screening and Diagnostics

OBJECTIVE: We aimed to investigate the validity of noninvasive prenatal diagnosis (NIPD) based on direct haplotype phasing without the proband or other family members and its feasibility for clinical application in the case of Duchenne muscular dystrophy (DMD). METHODS: Thirteen singleton-pregnancy families affected by DMD were recruited. The pathogenic variants in the pregnant females have been identified by multiplex ligation-dependent probe amplification (MLPA). We resolved maternal haplotypes for each family by performing targeted linked-read sequencing of their high molecular weight DNA, respectively. Then, we integrated the maternal haplotypes and the targeted sequencing results of maternal plasma DNA to infer the fetal haplotype and the DMD gene variant status. The fetal genotypes were further validated by using chorionic villus sampling. RESULTS: The method of directly resolving maternal haplotype through targeted linked-read sequencing was smoothly performed in 12 participated families, but one failed (F11). The predicted variant status of 12 fetuses was correct, which had been confirmed by invasive prenatal diagnosis. CONCLUSION: Direct haplotyping of NIPD based on linked-read sequencing for DMD is accurate.