title: How do keratinizing disorders and blistering disorders overlap?
abstract: Inherited keratinizing disorders are caused by mutations in the genes encoding cornified cell envelope proteins, enzymes and their inhibitors, adhesion molecules, cytoskeletal proteins and others in the epidermis. These molecules are known to regulate differentiation, proliferation and cell adhesions. Intriguingly, some keratinizing disorders show blistering skin lesions, while some inherited blistering disorders show abnormal keratinization. Therefore, hereditary keratinizing and blistering diseases are closely related and show overlapping genetic backgrounds. In this review, we overviewed keratinizing and blistering disorders in terms of overlapping of the two disease groups. Gene mutations in desmosomal components cause striate keratoderma, Naxos disease, epidermolytic palmoplantar keratoderma and plakophilin deficiency, which first show skin fragility and blisters and later hyperkeratosis. Gene mutations in hemidesmosomal components cause various forms of epidermolysis bullosa, some of which show hyperkeratosis on the nails, palms and soles, in addition to blister formation. Diseases with gene mutations in calcium pump proteins are Darier disease and Hailey-Hailey disease, which show clinicopathological overlaps and develop both keratinizing and blistering skin lesions. Finally, gene mutations in epidermal keratins cause epidermolysis bullosa simplex, epidermolytic ichthyosis, superficial epidermolytic ichthyosis, epidermolytic palmoplantar keratoderma and pachyonychia congenita/focal palmoplantar keratoderma, which show thickening of the palms and soles with underlying blister formation. In general, responsible proteins for diseases developing both keratinizing and blistering conditions are adhesion molecules, calcium pump proteins and keratins, but not connexins, cornified cell envelop proteins, enzymes or inhibitors. It is still unknown how particular keratinizing diseases develop blisters and vice versa.
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hamada
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tsuruta
authors.forename: Shunpei
authors.initials: S
authors.lastname: Fukuda
authors.forename: Norito
authors.initials: N
authors.lastname: Ishii
authors.forename: Kwesi
authors.initials: K
authors.lastname: Teye
authors.forename: Sanae
authors.initials: S
authors.lastname: Numata
authors.forename: Teruki
authors.initials: T
authors.lastname: Dainichi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Karashima
authors.forename: Chika
authors.initials: C
authors.lastname: Ohata
authors.forename: Minao
authors.initials: M
authors.lastname: Furumura
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics; D001768:Blister / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D004817:Epidermis / Q000378:metabolism / Q000473:pathology*; D004820:Epidermolysis Bullosa / Q000235:genetics; D006201:Hair Diseases / Q000235:genetics; D006801:Humans; D017488:Hyperkeratosis, Epidermolytic / Q000235:genetics*; D007633:Keratins / Q000235:genetics* / Q000502:physiology; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D009154:Mutation; D016506:Pemphigus, Benign Familial / Q000235:genetics; D012871:Skin Diseases / Q000235:genetics*
chemical_list: D007633:Keratins; D002118:Calcium