Haplotype-based non-invasive prenatal diagnosis of recessive dystrophic epidermolysis bullosa via targeted capture sequencing of maternal plasma.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and severe hereditary skin disease, caused by mutations in the COL7A1. However, whether non-invasive prenatal testing (NIPT) can be used for this monogenic genodermatosis remains unknown. Accordingly, we conducted a study in which one couple at high risk of having a fetus with RDEB were recruited and tested by haplotyping-based NIPT. Next-generation sequencing-based multi-gene panel testing was carried out in this couple and their first child as proband who was affected with RDEB. We deduced parental haplotypes via single nucleotide polymorphism (SNP)-based haplotype linkage analysis. Then the maternal plasma cell-free DNA was also sequenced to determine the fetal haplotypes using a parental haplotype-assisted hidden Markov model (HMM) analysis. Results show that the fetus was only a heterozygous mutation carrier in COL7A1 and the identical results were obtained after birth. These results demonstrate that haplotyping-based NIPT is a feasible method for NIPT of RDEB.