Verkerk, Annemieke JMH;
Andrei, Daniela;
Vermeer, Mathilde CSC;
Kramer, Duco;
Schouten, Marloes;
Arp, Pascal;
Verlouw, Joost AM;
... Bolling, Maria C; + view all
(2023)
Disruption of tuftelin 1, a desmosome associated protein, causes skin fragility, woolly hair and palmoplantar keratoderma.
Journal of Investigative Dermatology
10.1016/j.jid.2023.02.044.
(In press).
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Disruption of tuftelin 1, a desmosome associated protein, causes skin fragility, woolly hair and palmoplantar keratoderma |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jid.2023.02.044 |
| Publisher version: | https://doi.org/10.1016/j.jid.2023.02.044 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10180559 |
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