Homozygous Nonsense Mutation in DSC3 Resulting in Skin Fragility and Hypotrichosis
TLDR A boy's skin fragility and sparse hair were caused by a genetic mutation affecting skin cell adhesion.
Researchers identified a homozygous nonsense mutation in the DSC3 gene (c.2180T>G; p.Leu727*) in a 5-year-old boy from a consanguineous Egyptian family, leading to skin fragility and hypotrichosis. The patient exhibited trauma-induced blisters, sparse and fragile hair, and other skin abnormalities. Histological and ultrastructural analyses confirmed desmosome detachment and reduced desmosome numbers. Whole-exome sequencing revealed the mutation, and immunofluorescence microscopy showed a complete absence of DSC3 labeling. Quantitative real-time PCR indicated upregulation of other desmosomal components. This study provided definitive evidence that DSC3 loss causes skin fragility and hypotrichosis, expanding the understanding of desmosomal genodermatoses.
