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Mutations in PERP Cause Dominant and Recessive Keratoderma
- Source :
- Journal of Investigative Dermatology, Journal of Investigative Dermatology, Nature Publishing Group, 2019, 139, pp.380-390. ⟨10.1016/j.jid.2018.08.026⟩, Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Investigation of genetic determinants of Mendelian skin disorders has substantially advanced understanding of epidermal biology. Here we show that mutations in PERP, encoding a crucial component of desmosomes, cause both dominant and recessive human keratoderma. Heterozygosity for a C-terminal truncation, which produces a protein that appears to be unstably incorporated into desmosomes, causes Olmsted syndrome with severe periorificial and palmoplantar keratoderma in multiple unrelated kindreds. Homozygosity for an N-terminal truncation ablates expression and causes widespread erythrokeratoderma, with expansion of epidermal differentiation markers. Both exhibit epidermal hyperproliferation, immature desmosomes lacking a dense midline observed via electron microscopy, and impaired intercellular adhesion upon mechanical stress. Localization of other desmosomal components appears normal, which is in contrast to other conditions caused by mutations in genes encoding desmosomal proteins. These discoveries highlight the essential role of PERP in human desmosomes and epidermal homeostasis and further expand the heterogeneous spectrum of inherited keratinization disorders.
- Subjects :
- Adult
Male
0301 basic medicine
Heterozygote
[SDV]Life Sciences [q-bio]
DNA Mutational Analysis
Dermatology
Biology
Biochemistry
Article
Loss of heterozygosity
Young Adult
03 medical and health sciences
symbols.namesake
0302 clinical medicine
Keratoderma, Palmoplantar
Keratin
Cell Adhesion
medicine
Humans
Genes, Tumor Suppressor
Child
Frameshift Mutation
Keratoderma
Molecular Biology
Gene
chemistry.chemical_classification
integumentary system
Homozygote
Membrane Proteins
Desmosomes
Exons
Cell Biology
medicine.disease
Cell biology
Microscopy, Electron
030104 developmental biology
Palmoplantar keratoderma
chemistry
OLMSTED SYNDROME
Codon, Nonsense
Child, Preschool
030220 oncology & carcinogenesis
Mendelian inheritance
symbols
Female
Epidermis
Intracellular
Subjects
Details
- ISSN :
- 0022202X and 15231747
- Volume :
- 139
- Database :
- OpenAIRE
- Journal :
- Journal of Investigative Dermatology
- Accession number :
- edsair.doi.dedup.....a1881eb74feafba970319d94afe510fa