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

Abstract

Objective We aimed to investigate the validity of noninvasive prenatal diagnosis (NIPD) based on direct haplotype phasing without the proband and its feasibility for clinical application in the case of Duchenne Muscular Dystrophy (DMD). Methods Thirteen singleton-pregnancy families affected by DMD were recruited.Firstly, we resolved maternal haplotypes for each family by performing targeted linked-read sequencing of their high molecular weight DNA, respectively. Then, we identified SNPs of the DMD gene in all carrier mothers and inferred the DMD gene mutation status of all fetuses. Finally, the fetal genotypes were further validated by using chorionic villus sampling. ResultsThe method of directly resolving maternal haplotype through targeted linked-read sequencing was smoothly performed in all participated families. The predicted mutational status of 13 fetuses was correct, which had been confirmed by invasive prenatal diagnosis. ConclusionDirect haplotyping of NIPD based on linked-read sequencing for DMD is accurate.

Noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and Bayesian approach

“…We managed haplotype phasing of sequences with a mean length of 129 kb around the expansions in 23/28 parents. The phase block size across the target region was smaller compared with the studies by Chen et al 18 and Lee et al 10 who reported phase blocks with of a mean size of 741 and 632 kb, respectively. Their higher phasing success was mainly due to the larger width of the targeted sequencing region (657 kb and 3.2 Mb, respectively).…”

Accuracy of Non-Invasive Prenatal Testing for Duchenne Muscular Dystrophy in Families at Risk: A Systematic Review

“…It affects 1 in 3500 newborn males. The onset usually occurs in early childhood before the age of three and patients rarely outlive the age of twenty [3][4][5]. The development of NIPT techniques for Duchenne muscular dystrophy as an X-linked disease presented a substantial challenge as a consequence of high levels of maternally derived mutant alleles that outnumber potentially mutated alleles of fetal origin in maternal plasma.…”

A feasibility study of noninvasive prenatal diagnosis in facioscapulohumeral muscular dystrophy type 1 in a Chinese family

“…Therefore, NIPD is almost no risk for the pregnant women and fetuses, and has been gradually applied in fetal aneuploidy, monogenic diseases, sex-linked genetic diseases, and so on ( Xu et al, 2015 ; Drury et al, 2016 ; Guseh, 2020 ). In recent years, haplotype-based NIPD has been reported to be able to deduce the inheritance status of variants in fetuses accurately ( Hui et al, 2017 ; Ma et al, 2017 ; Chen et al, 2020 ). However, NIPD of FSHD1 has not yet been reported.…”