Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, China.
State Key Laboratory of Genetic Engineering and MOE Engineering Research Center of Gene Technology, School of Life Sciences, Fudan University, Shanghai, China.
J Dermatol. 2023 Jul;50(7):946-950. doi: 10.1111/1346-8138.16760. Epub 2023 Mar 7.
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.
隐性营养不良型大疱性表皮松解症（RDEB）是一种罕见且严重的遗传性皮肤疾病，由 COL7A1 基因突变引起。然而，非侵入性产前检测（NIPT）是否可用于这种单基因遗传性皮肤病尚不清楚。因此，我们进行了一项研究，招募了一对具有 RDEB 胎儿高风险的夫妇，并进行基于单体型的 NIPT 检测。对这对夫妇及其患有 RDEB 的先证者第一胎进行了基于下一代测序的多基因panel 检测。通过基于单核苷酸多态性（SNP）的单体型连锁分析推断出父母的单体型。然后对母体无细胞游离 DNA 进行测序，使用基于双亲单体型的隐马尔可夫模型（HMM）分析来确定胎儿单体型。结果表明，胎儿仅为 COL7A1 的杂合突变携带者，出生后获得了相同的结果。这些结果表明，基于单体型的 NIPT 是 RDEB NIPT 的一种可行方法。
