Novel Haplotype-Based Noninvasive Prenatal Diagnosis for Recessive Single-Gene Disorders: A Proof-of-Concept Study.

DiHNIPD: parental haplotyping by stLFR-WGS + HMM/Viterbi model to infer fetal genotype from maternal plasma DNA

DiHNIPD (direct haplotyping-based NIPD) uses stLFR-WGS to reconstruct parental haplotypes, then infer fetal genotype for recessive disorders from maternal plasma. Tested in 23 at-risk couples, it achieves 100% concordance with invasive diagnosis. This approach simplifies family prerequisites of standard NIPD (no affected family member required) and is less costly than targeted NGS methods.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This proof of concept is promising for NIPD of common recessive disorders (hemoglobinopathies, cystic fibrosis, metabolic diseases). Dependence on stLFR-WGS (BGI technology) limits immediate generalization, but the HMM algorithm is transferable to other long-read platforms. Worth monitoring for larger-scale validation.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 2/2 · Sample size: 0/1 · Publication status: 0/1 → Total: 6/10