A new study published in Prenatal Diagnosis investigated 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). The present study selected 13 singleton-pregnancy families affected by DMD. The pathogenic variants in pregnant females were identified by multiplex ligation-dependent probe amplification (MLPA). Maternal haplotypes for each family were resolved by performing targeted linked-read sequencing of their high molecular weight DNA. The maternal haplotypes and targeted sequencing results of maternal plasma DNA were then integrated, to infer the fetal haplotype and DMD gene variant status. The fetal genotypes were further validated by using chorionic villus sampling. It was noted that this method of directly resolving maternal haplotype through targeted linked-read sequencing was smoothly performed in twelve participated families; however, one failed (F11). The predicted variant status of 12 fetuses was correct, which was confirmed by invasive prenatal diagnosis. Therefore, it was concluded that direct haplotyping of NIPD based on linked-read sequencing for DMD is accurate.

Source: Prenatal Diagnosis. 2020 Jan 9. doi: 10.1002/pd.5641