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

Abstract

AbstractRecessive 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.