title: Update on autosomal recessive congenital ichthyosis: mRNA analysis using hair samples is a powerful tool for genetic diagnosis.
abstract: Research on the molecular genetics and pathomechanisms of autosomal recessive congenital ichthyosis (ARCI) has advanced considerably and several causative genes and molecules underlying the disease have been identified. Three major ARCI phenotypes are harlequin ichthyosis (HI), lamellar ichthyosis (LI), and congenital ichthyosiform erythroderma (CIE). Skin barrier defects are involved in the pathogenesis of ARCI. In this review, the causative genes of ARCI and its phenotypes as well as recent advances in the field are summarized. The known causative molecules underlying ARCI include ABCA12, TGM1, ALOXE3, ALOX12B, NIPAL4, CYP4F22, PNPLA1, CERS3, and LIPN. It is important to examine genetic associations and to elucidate the pathomechanisms of ARCI to establish effective therapies and beneficial genetic counseling. Next-generation sequencing is a promising method that enables the detection of causative disease mutations, even in cases of unexpected concomitant genetic diseases. For genetic diagnosis, obtaining mRNA from hair follicle epithelial cells, which are analogous to keratinocytes in the interfollicular epidermis, is convenient and minimally invasive in patients with ARCI. We confirmed that our mRNA analysis method using hair follicle samples can be applied not only to keratinization disorders, but also to other genetic diseases in the dermatology field. Studies that suggest potential next-generation therapies using ARCI model mice are also reviewed.
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Sugiura
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: makiyama@med.nagoya-u.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005808:Genes, Recessive; D005820:Genetic Testing / Q000379:methods; D006197:Hair / Q000737:chemistry*; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000175:diagnosis / Q000235:genetics*; D017490:Ichthyosis, Lamellar / Q000175:diagnosis / Q000235:genetics*; D008049:Lipase / Q000235:genetics; D008084:Lipoxygenase / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D011956:Receptors, Cell Surface / Q000235:genetics; D051049:Sphingosine N-Acyltransferase / Q000235:genetics; D011503:Transglutaminases / Q000235:genetics; D000217:Acyltransferases; D010740:Phospholipases
chemical_list: D018528:ATP-Binding Cassette Transporters; D001092:Arachidonate 12-Lipoxygenase; D003577:Cytochrome P-450 Enzyme System; D008049:Lipase; D008084:Lipoxygenase; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051049:Sphingosine N-Acyltransferase; D011503:Transglutaminases; C473801:ABCA12 protein, human; C499859:NIPAL4 protein, human; C559989:CYP4F22 protein, human; C511051:ALOXE3 protein, human; C514086:ALOX12B protein, human; C583317:CERS3 protein, human; C105804:transglutaminase 1; C549684:PNPLA1 protein, human; D000217:Acyltransferases; D010740:Phospholipases
keywords: ABCA12 promoter; Autosomal recessive congenital ichthyosis; Congenital ichthyosiform erythroderma; Hair samples; Harlequin ichthyosis; Lamellar ichthyosis