@article {734,
	title = {Mutations in PERP Cause Dominant and Recessive Keratoderma.},
	journal = {J Invest Dermatol},
	volume = {139},
	year = {2019},
	month = {2019 02},
	pages = {380-390},
	abstract = {<p>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.</p>},
	issn = {1523-1747},
	doi = {10.1016/j.jid.2018.08.026},
	author = {Duchatelet, Sabine and Boyden, Lynn M and Ishida-Yamamoto, Akemi and Zhou, Jing and Guibbal, Laure and Hu, Ronghua and Lim, Young H and Bole-Feysot, Christine and Nitschk{\'e}, Patrick and Santos-Simarro, Fernando and de Lucas, Raul and Milstone, Leonard M and Gildenstern, Vanessa and Helfrich, Yolanda R and Attardi, Laura D and Lifton, Richard P and Choate, Keith A and Hovnanian, Alain}
}
