Haplotype-based approach for noninvasive prenatal tests of Duchenne muscular dystrophy using cell-free fetal DNA in maternal plasma

TY - JOUR

T1 - Haplotype-based approach for noninvasive prenatal tests of Duchenne muscular dystrophy using cell-free fetal DNA in maternal plasma

AU - Xu, Yan

AU - Li, Xuchao

AU - Ge, Hui-Juan

AU - Xiao, Bing

AU - Zhang, Yan-Yan

AU - Ying, Xiao-Min

AU - Pan, Xiao-Yu

AU - Wang, Lei

AU - Xie, Wei-Wei

AU - Ni, Lin

AU - Chen, Sheng-Pei

AU - Jiang, Wen-Ting

AU - Liu, Ping

AU - Ye, Hui

AU - Cao, Ying

AU - Zhang, Jing-Min

AU - Liu, Yu

AU - Yang, Zu-Jing

AU - Chen, Ying-Wei

AU - Chen, Fang

AU - Jiang, Hui

AU - Ji, Xing

PY - 2015/11/1

Y1 - 2015/11/1

N2 - This study demonstrates noninvasive prenatal testing (NIPT) for Duchenne muscular dystrophy (DMD) using a newly developed haplotype-based approach. Methods: Eight families at risk for DMD were recruited for this study. Parental haplotypes were constructed using target-region sequencing data from the parents and the probands. Fetal haplotypes were constructed using a hidden Markov model through maternal plasma DNA sequencing. The presence of haplotypes linked to the maternal mutant alleles in males indicated affected fetuses. This method was further validated by comparing the inferred single-nucleotide polymorphism (SNP) genotypes to the direct sequencing results of fetal genomic DNA. Prenatal diagnosis was confirmed with amniocentesis, and those results were interpreted in a blinded fashion. Results: The results showed an average accuracy of 99.98% for the total inferred maternal SNPs. With a mean depth of 30 × achieved in the 10-Mb target region of each sample, the noninvasive results were consistent with those of the invasive procedure.Conclusion:This is the first report of NIPT for DMD and the first application of a haplotype-based approach in NIPT for X-linked diseases. With further improvements in accuracy, this haplotype-based strategy could be feasible for NIPT for DMD and even other X-linked single-gene disorders.

AB - This study demonstrates noninvasive prenatal testing (NIPT) for Duchenne muscular dystrophy (DMD) using a newly developed haplotype-based approach. Methods: Eight families at risk for DMD were recruited for this study. Parental haplotypes were constructed using target-region sequencing data from the parents and the probands. Fetal haplotypes were constructed using a hidden Markov model through maternal plasma DNA sequencing. The presence of haplotypes linked to the maternal mutant alleles in males indicated affected fetuses. This method was further validated by comparing the inferred single-nucleotide polymorphism (SNP) genotypes to the direct sequencing results of fetal genomic DNA. Prenatal diagnosis was confirmed with amniocentesis, and those results were interpreted in a blinded fashion. Results: The results showed an average accuracy of 99.98% for the total inferred maternal SNPs. With a mean depth of 30 × achieved in the 10-Mb target region of each sample, the noninvasive results were consistent with those of the invasive procedure.Conclusion:This is the first report of NIPT for DMD and the first application of a haplotype-based approach in NIPT for X-linked diseases. With further improvements in accuracy, this haplotype-based strategy could be feasible for NIPT for DMD and even other X-linked single-gene disorders.

U2 - 10.1038/gim.2014.207

DO - 10.1038/gim.2014.207

M3 - Journal article

C2 - 25654318

SN - 1098-3600

VL - 17

SP - 889

EP - 896

JO - Genetics In Medicine

JF - Genetics In Medicine

IS - 11

ER -