title: An update on molecular aspects of the non-syndromic ichthyoses.
abstract: Ichthyosis includes a number of subtypes from congenital severe forms, such as harlequin ichthyosis (HI), to mild non-congenital forms, such as ichthyosis vulgaris. Recently, research into the pathomechanisms of ichthyoses has dramatically advanced and led to the identification of several causative genes and molecules underlying the genetic defects. In most types of ichthyosis, pathogenic mechanisms are associated with defects in skin barrier function. Three major components of the stratum corneum barrier are (i) intercellular lipid layers, (ii) cornified cell envelope and (iii) keratin-filaggrin degradation products. The causative molecules underlying ichthyosis subtypes include ABCA12, lipoxygenase-3, 12R-lipoxygenase, CYP4F2 homolog, ichthyin and steroid sulphatase and all these are thought to be related to the intercellular lipid layers. Transglutaminase 1 has a function in cornified cell envelope formation. Keratins 1, 10 and 2 are involved in the keratin network of suprabasal keratinocytes and filaggrin are essential for formation of keratohyalin granules. In fact, loss of ABCA12 function leads to a defective lipid barrier in the stratum corneum, resulting in the HI phenotype and ABCA12 is a known keratinocyte lipid transporter associated with lipid transport in lamellar granules. Filaggrin gene mutations in ichthyosis vulgaris cause keratohyalin granule deficiency. Information concerning genetic defects and ichthyotic disease pathomechanisms are beneficial to develop effective therapy and provide information for genetic counselling including prenatal diagnosis for families affected by ichthyotic disease.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. akiyama@med.hokudai.ac.jp
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072470:Cytochrome P450 Family 4; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007057:Ichthyosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D007381:Intermediate Filament Proteins / Q000235:genetics; D007633:Keratins / Q000235:genetics; D008084:Lipoxygenase / Q000235:genetics; D009154:Mutation; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011956:Receptors, Cell Surface / Q000235:genetics; D012867:Skin / Q000378:metabolism / Q000503:physiopathology*; D012879:Skin Physiological Phenomena; D043266:Steryl-Sulfatase / Q000235:genetics; D011503:Transglutaminases / Q000235:genetics
chemical_list: C473801:ABCA12 protein, human; D018528:ATP-Binding Cassette Transporters; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; C499859:NIPAL4 protein, human; D011956:Receptors, Cell Surface; D007633:Keratins; D003577:Cytochrome P-450 Enzyme System; D008084:Lipoxygenase; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; D011503:Transglutaminases; C105804:transglutaminase 1; D043266:Steryl-Sulfatase