Case Report: Bi-allelic missense variant in the desmocollin 3 gene causes hypotrichosis and recurrent skin vesicles.

Hypotrichosis with Recurrent Skin Vesicles (HYPTSV) is an extremely rare condition, having autosomal recessive inheritance. Here in we report a 4-years- old Saudi boy who presented with a history of recurrent skin blisters that are localized to the extremities and hypotrichosis since birth. The present study describes a consanguineous Saudi family segregating HYPTSV in an autosomal recessive fashion. A single proband (II-1) exhibited features such as diffused non-scarring alopecia on the scalp, intraepidermal blister, post-inflammatory hyperpigmented macules, and follicular hyperkeratosis. DNA of the index was subjected to whole-genome sequencing (WGS). Furthermore, 3D protein modeling was performed for the mutated and normal protein. WGS revealed a novel bi-allelic missense variant (c.154G>C; p. Val52Leu) in the gene, which segregated perfectly using Sanger sequencing. In addition, 3D protein modeling revealed a substantial change in the mutated DSC3 protein as compared to the normal DSC3 protein. This is the 3rd novel variant reported in the gene associated with the HYPTSV phenotype. This report further strengthens the evidence that bi-allelic variants in the cause severe HYPTSV in humans.