COL7A1 Homozygous Arg2471Ter Mutation Leads to the Severe Phenotype of Autosomal Recessive Dystrophic Epidermolysis Bullosa in the Fetus

[摘要] Introduction: Autosomal recessive dystrophic epidermolysis bullosa (RDEB) is a rare disease with an early onset and severe phenotype. The pathogenic mechanism associated with mutations in the gene COL7A1 has been widely studied and many related cases have been reported, but prenatal cases are rare. Here, we report the prenatal diagnosis of a sporadic case of RDEB. Methods: In this study, the fetus with abnormal skin manifestations, which were determined during a prenatal ultrasound, was evaluated based on the ultrasound and autopsy findings and the results of molecular diagnostic analyses. Samples of the fetus and the parents were subjected to trio whole-exome sequencing, and in vitro functional analyses were conducted to analyze the pathogenicity of the detected mutation. Results: During the conventional prenatal ultrasound, the fetus showed abnormal epidermal lines on both lower limbs and the plantar skin as well as an interruption of the continuity of the lateral epidermal line below the ankle of the right lower limb. Gene testing revealed a homozygous nonsense mutation in COL7A1T, p.Arg2471Ter), which gave rise to RDEB in the fetus. Further, the results of the in vitro functional experiments confirmed that the mutation might lead to protein degradation. Conclusion: Most prenatal diagnoses of RDEB are the result of targeted molecular analyses carried out based on family history, and prenatal ultrasound reports of severe RDEB phenotypes are extremely rare. Our case suggests that the observation of abnormal epidermal lines should be given due consideration during prenatal diagnosis, as they may be a sign of possible epidermolysis bullosa.

[学科分类] 基础医学

[关键词] Prenatal diagnosis;Whole-exome sequencing;COL7A1;Recessive dystrophic epidermis bullosa;Homozygous mutation