Author/Editor		Chamcheu, Jean Christopher; Siddiqui, Imtiaz A; Syed, Deeba N; Adhami, Vaqar M; Liović, Mirjana; Mukhtar, Hasan
Title		Keratin gene mutations in disorders of human skin and its appendages
Type		članek
Source		Arch Biochem Biophys
Vol. and No.		Letnik 508, št. 2
Publication year		2011
Volume		str. 123-37
Language		eng
Abstract		Keratins, the major structural protein of all epithelia, are a diverse group of cytoskeletal scaffolding proteins that form intermediate filament networks, providing structural support to keratinocytes that maintain the integrity of the skin. Expression of keratin genes is usually regulated by differentiation of the epidermal cells within the stratifying squamous epithelium. Amongst the 54 known functional keratin genes in humans, about 21 different genes including hair and hair follicle-specific keratins have been associated with diverse hereditary disorders. The exact phenotype of each disease mostly reflects the spatial level of expression and types of the mutated keratin genes, the positions of the mutations as well as their consequences at sub-cellular levels. The identification of specific mutations in keratin disorders is the basis of our understanding that lead to reclassification, improved diagnosis with prognostic implications, prenatal testing and genetic counseling in severe cutaneous keratin genodermatoses. A disturbance in cutaneous keratins as a result of mutation(s) in the gene(s) that encode keratin intermediate filaments (KIF) causes keratinocytes and cutaneous tissue fragility, accounting for a large number of genetic disorders in human skin and its appendages. These diseases are characterized by a loss of structural integrity in keratinocytes expressing mutated keratins in vivo, often manifested as keratinocytes fragility (cytolysis), intra-epidermal blistering, hyperkeratosis, and keratin filament aggregation in severely affected tissues. Examples include epidermolysis bullosa simplex (EBS), keratinopathic ichthyosis (KPI), pachyonychia congenital (PC), monilethrix, steatocystoma multiplex and ichthyosis bullosa of Siemens (IBS). These keratins also have been identified to have roles in cell growth, apoptosis, tissue polarity, wound healing and tissue remodeling.
Descriptors		SKIN DISEASES KERATIN EPIDERMIS INTERMEDIATE FILAMENT PROTEINS KERATINOCYTES MUTATION EPIDERMOLYSIS BULLOSA EPIDERMOLYSIS BULLOSA SIMPLEX HAIR DISEASES NAIL DISEASES ICHTHYOSIS