Traditional and novel genes associated with skin fragility syndrome


Desmosomes are cell-cell adhesion junctions that anchor intermediate filaments to the plasma membrane, providing mechanical resilience to tissues that undergo high intensities of mechanical stretch, such as skin and heart. Although the first desmosomal components were discovered sixty years ago, the most recent studies show that there are newly identified proteins, that have a crucial role in the desmosome structure or their signaling. In this regard, this thesis of Daniela Andrei aims to characterize a novel gene associated with the desmosome, tuftelin 1 (TUFT1), encoding the protein TUFT1.

The significance of desmosomes is further emphasized by pathogenic variants in desmosomal genes which result in a spectrum of skin fragility and hyperkeratosis phenotypes that also may affect hair or heart. However, oftentimes these variants are in silico analyzed, predicting inaccurate results, leaving the genotype-phenotype correlation poorly understood. Therefore, another aim of this thesis was to functionally analyze the pathogenic variants found in desmoplakin (DSP) gene, involved in skin fragility and cardiocutaneous syndrome, underlining the molecular pathology and phenotypes associated with desmosomal dysfunction.