AUTHOR=Al Hawsawi Khalid , Al Jabri Mazin , Dajam Mazen S. , Almahdi Bashaer , Alhawsawi Waseem K. , Abbas Safdar , Al Tuwaijri Abeer , Umair Muhammad , Alfadhel Majid , Al-Khenaizan Sultan 

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

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.994509

DOI=10.3389/fgene.2022.994509

ISSN=1664-8021

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