Mutations in PERP Cause Dominant and Recessive Keratoderma
| العنوان: | Mutations in PERP Cause Dominant and Recessive Keratoderma |
|---|---|
| المؤلفون: | Vanessa Gildenstern, Keith A. Choate, Young H. Lim, Patrick Nitschké, Alain Hovnanian, Yolanda R. Helfrich, Richard P. Lifton, Christine Bole-Feysot, S. Duchatelet, Raúl de Lucas, Leonard M. Milstone, Lynn M. Boyden, Laura D. Attardi, Fernando Santos-Simarro, Laure Guibbal, Akemi Ishida-Yamamoto, Jing Zhou, Ronghua Hu |
| المساهمون: | Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Yale University School of Medicine, Asahikawa Medical College, University of Michigan System, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University |
| المصدر: | 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 |
| بيانات النشر: | Elsevier BV, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 0022-202X 1523-1747 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a1881eb74feafba970319d94afe510fa https://doi.org/10.1016/j.jid.2018.08.026 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a1881eb74feafba970319d94afe510fa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 0022202X 15231747 |
|---|