Coinheritance of 2 New Potentially Damaging Heterozygous COL7A1 Variants in a Family With Autosomal Dominant Epidermolysis Bullosa Pruriginosa

Abstract

Epidermolysis bullosa pruriginosa (EBP) is a rare subtype of EB which is characterized by intense pruritus with blistering and nodular or lichenoid lesions most prominent on the lower extremities. It is caused by variants in COL7A1 which encodes for type VII collagen. There is wide phenotypic and genotypic variability between affected individuals. We report 2 potentially pathogenic variants in COL7A1 occurring on the same allele in a family with EBP and autosomal dominant inheritance. Late-onset EBP and incomplete penetrance may lead to delayed presentation in affected family members with the same variants. The broad phenotypic variability seen in EBP suggests that further genotypic and environmental factors may influence presentation. Genetic and histopathological diagnosis is essential, given the considerable overlap with clinically similar presentations such as hypertrophic lichen planus.

Phenotype and genotype correlation of inherited epidermolysis bullosa in Indonesia

“…Interestingly, despite the variability of clinical manifestations, there was co‐inheritance of two similar missense variants in COL7A1 in all five family members. Hale et al also described two pathogenic variants in COL7A1 in a family with EB pruriginosa with a similar variable presentation 5 . This variability in clinical manifestations suggests possible epigenetic or external influences, for example nutrition and environment.…”

“…Hale et al also described two pathogenic variants in COL7A1 in a family with EB pruriginosa with a similar variable presentation. 5 This variability in clinical manifestations suggests possible epigenetic or external influences, for example nutrition and environment.…”