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Noninvasive prenatal diagnosis for Duchenne muscular dystrophy based on the direct haplotype phasing
Author(s) -
Chen Min,
Chen Chao,
Huang Xiaoyan,
Sun Jun,
Jiang Lu,
Li Yingting,
Zhu Yaping,
Tian Changgeng,
Li Yufan,
Lu Zhe,
Wang Yaoshen,
Zeng Fanwei,
Yang Yun,
Song Xiwei,
Peng Zhiyu,
Yin Chenghong,
Chen Dunjin
Publication year - 2020
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.5641
Subject(s) - haplotype , proband , duchenne muscular dystrophy , multiplex ligation dependent probe amplification , chorionic villus sampling , prenatal diagnosis , genetics , medicine , multiplex , pregnancy , biology , genotype , fetus , mutation , gene , exon
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.