@misc{han_chen_guo_ye_peng_qiu_wang_li_zhang_liang_et al._2018, 
  title={Noninvasive prenatal test of methylmalonic academia cblC type through targeted sequencing of cell-free DNA in maternal plasma}, 
  DOI={10.1101/425918}, 
  abstractNote={<jats:title>Abstract</jats:title><jats:p>Methylmalonic acidemia (MMA) cblC type is the most frequent inborn error of intracellular cobalamin metabolism which is caused by mutations of <jats:italic>MMACHC</jats:italic> gene. Non-invasive test of MMA for pregnant women facilitates safe and timely prenatal diagnosis of the disease. In our study, we aimed to design and validate a haplotype-based noninvasive prenatal test (NIPT) method for cblC type of MMA. Targeted capture sequencing using customized hybridization was performed utilizing gDNA (genomic DNA) of trios including parents and an affected proband to determine parental haplotypes associated with the mutant and wild allele. The fetal haplotype was inferred later based on the high depth sequencing data of maternal plasma as well as haplotype linkage analysis. The fetal genotypes deduced by NIPT were further validated by amniocentesis. Haplotype-based NIPT was successfully performed in 21 families. The results of NIPT of 21 families were all consistent with invasive prenatal diagnosis, which was interpreted in a blinded fashion. Three fetuses were identified as compound heterozygosity of <jats:italic>MMACHC</jats:italic>, 9 fetuses were carriers of <jats:italic>MMACHC</jats:italic> variant, and 9 fetuses were normal. These results indicated that the haplotype-based NIPT for MMA through small target capture region sequencing is technically accurate and feasible.</jats:p>}, 
  publisher={Cold Spring Harbor Laboratory}, 
  author={Han, Lianshu and Chen, Chao and Guo, Fengyu and Ye, Jun and Peng, Zhiyu and Qiu, Wenjuan and Wang, Yaoshen and Li, Wei and Zhang, Huiwen and Liang, Lili and et al.}, 
  year={2018}, 
  month={Sep}
  }