biostudies-literatureZhang LThe Shanghai Municipal Science and Technology CommissionShanghai Hospital Development Center FoundationThe National Natural Science Foundation of ChinaThe Opening Project of Shanghai Key Laboratory of Embryo Original Diseases4https://www.ebi.ac.uk/biostudies/studies/S-EPMC12797552biostudies-literatureUnknown18(1)<h4>Background</h4>Noninvasive prenatal screening for aneuploidies and microdeletion/microduplication syndromes (MMS) has gained widespread clinical application. However, the development of noninvasive prenatal diagnosis for monogenic disorders (NIPT-M) has progressed slower. Existing NIPT-M approaches often require specialized designs, are limited to a narrow range of genes, or are expensive and impractical for clinical implementation.<h4>Methods</h4>We present HaploNIPD, a universal haplotype-based approach for NIPT-M, utilizing a targeted capture panel that includes 120,000 selected single-nucleotide polymorphisms. Maternal cell-free DNA (cfDNA) and genomic DNA (gDNA) from family members were targeted captured and massively parallel sequenced. Parental haplotypes were phased, and fetal Genome medicineUniversal noninvasive prenatal diagnosis for monogenic disorders using cell-free plasma DNA.PMC12797552No. 8241687shelab20240422Y11906700SHDC12026127Yang JHan XZhang LHua RXu HWang JZhao XLi NLi SGao LChen YFei HChang CWang YWu YfalseUniversal noninvasive prenatal diagnosis for monogenic disorders using cell-free plasma DNA.<h4>Background</h4>Noninvasive prenatal screening for aneuploidies and microdeletion/microduplication syndromes (MMS) has gained widespread clinical application. However, the development of noninvasive prenatal diagnosis for monogenic disorders (NIPT-M) has progressed slower. Existing NIPT-M approaches often require specialized designs, are limited to a narrow range of genes, or are expensive and impractical for clinical implementation.<h4>Methods</h4>We present HaploNIPD, a universal haplotype-based approach for NIPT-M, utilizing a targeted capture panel that includes 120,000 selected single-nucleotide polymorphisms. Maternal cell-free DNA (cfDNA) and genomic DNA (gDNA) from family members were targeted captured and massively parallel sequenced. Parental haplotypes were phased, and fetal 2025-01-01T00:00:00Z2025 Dec2026-06-09T05:34:32.129Z2026-06-09T03:07:28.368ZS-EPMC127975524134587310.1186/s13073-025-01588-5