Autosomal dominant <i>SLURP1</i> variants cause palmoplantar keratoderma and progressive symmetric erythrokeratoderma
Our results expand the phenotypic spectrum of EDD due to SLURP1 pathogenic variants. While autosomal recessive Mal de Meleda is due to biallelic loss-of-function SLURP1 variants, our finding of autosomal dominant SLURP1 pathogenic variants in kindreds with PPK and PSEK suggests a novel mechanism of action. We found that heterozygous p.A22V and p.A22D SLURP1 variants append two amino acids to secreted SLURP1, increase differentiation-induced SLURP1 expression and secretion and upregulate NF-κB signalling in people with PSEK.
Authors
- Christopher G. Bunick (ORCID: https://orcid.org/0000-0002-4011-8308)
- Ivan B. Lomakin (ORCID: https://orcid.org/0000-0001-6528-5068)
- Jing Zhou (ORCID: https://orcid.org/0000-0001-6601-4446)
- Ryland D. Mortlock (ORCID: https://orcid.org/0000-0001-9666-4394)
- Maria-Laura Cossio (ORCID: https://orcid.org/0000-0003-0202-3954)
- Rong‐Hua Hu (ORCID: https://orcid.org/0000-0002-5260-2519)
- Xingyuan Jiang (ORCID: https://orcid.org/0000-0002-9891-6353)
- Keith Choate
Institutions
- Pontificia Universidad Católica de Chile (CL)
- Yale University (US)
Publication Details
- Journal
- British Journal of Dermatology
- Published
- 2025-02-06
- DOI
- https://doi.org/10.1093/bjd/ljaf049
- Citations
- 2
- Primary Topic
- Connexins and lens biology
- Type
- article
- Field-Weighted Citation Impact
- 1.61