| Experiment Id | GSE237986 | Name | Disruption of tuftelin 1, a desmosome associated protein,causes skin fragility, woolly hair and palmoplantar keratoderma |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2024-11-26 |
| description | Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss of function variants in desmosomal genes lead to a variety of skin and heart related phenotypes. Here, we report tuftelin 1 as a desmosome-associated protein, implicated in epidermal integrity. In two siblings with mild skin fragility, woolly hair and mild palmoplantar keratoderma, but without a cardiac phenotype, we identified a homozygous splice site variant in the TUFT1 gene, leading to aberrant mRNA splicing and loss of tuftelin 1 protein. Patients' skin and keratinocytes showed acantholysis, perinuclear retraction of intermediate filaments, and reduced mechanical stress resistance. Immunolabeling and transfection studies showed that tuftelin 1 is positioned within the desmosome and its location dependent on the presence of the desmoplakin carboxy-terminal tail. A Tuft1 knock-out mouse model mimicked the patients' phenotypes. Altogether, this study reveals tuftelin 1 as a desmosome-associated protein, whose absence causes skin fragility, woolly hair and palmoplantar keratoderma. Total RNA was isolated from 4 wildtype and 3 healthy-looking TUFT1 knock out mouse skin sections and RNA seq was performed on these samples. Differential expression analysis was determined on knockouts over controls, and FDR<0.05 differentially expressed genes were extracted. |
