Abstract
Background:
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.
Methods:
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.
Results:
WGS revealed a novel bi-allelic missense variant (c.154G>C; p. Val52Leu) in the
DSC3
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.
Conclusion:
This is the 3rd novel variant reported in the
DSC3
gene associated with the HYPTSV phenotype. This report further strengthens the evidence that bi-allelic variants in the
DSC3
cause severe HYPTSV in humans.