title: Hepoxilin A3 (HXA3) synthase deficiency is causative of a novel ichthyosis form.
abstract: Non-bullous congenital ichthyosis erythroderma (NCIE) and lamellar ichthyosis (LI) are characterized by mutations in 12R-lipoxygenase (12R-LOX) and/or epidermal lipoxygenase 3 (eLOX3) enzymes. The eLOX3 lacks oxygenase activity, but is capable of forming hepoxilin-type products from arachidonic acid-derived hydroperoxide from 12R-LOX, termed 12R-hydroperoxyeicosa-5,8,10,14-tetraenoic acid (12R-HpETE). Mutations in either of two enzymes lead to NCIE or LI. Moreover, 12R-LOX-deficient mice exhibit severe phenotypic water barrier dysfunctions. Here, we demonstrate that 12R-HpETE can also be transformed to 8R-HXA(3) by hepoxilin A(3) (HXA(3)) synthase (12-lipoxygenase), which exhibits oxygenase activity. We also presented a novel form of ichthyosis in a patient, termed hepoxilin A(3) synthase-linked ichthyosis (HXALI), whose scales expressed high levels of 12R-LOX, but were deficient of HXA(3) synthase.
authors: Eicosanoid and Lipid Research Division, Centre for Experimental Gynecology and Breast Research, Charité, University Medical Centre Benjamin Franklin, Berlin, Germany.
authors: Santosh
authors: S
authors: Nigam
authors: Maria-Patapia
authors: MP
authors: Zafiriou
authors: Rupal
authors: R
authors: Deva
authors: Nadja
authors: N
authors: Kerstin
authors: Christoph
authors: C
authors: Geilen
authors: Roberto
authors: R
authors: Ciccoli
authors: Marco
authors: M
authors: Sczepanski
authors: Maren
authors: M
authors: Lohse
mesh_terms: D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000201:enzymology* / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D008084:Lipoxygenase / Q000235:genetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D011994:Recombinant Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D011994:Recombinant Proteins; D008084:Lipoxygenase; C518403:eLOX3 protein, mouse; D001092:Arachidonate 12-Lipoxygenase; D019746:Intramolecular Oxidoreductases; C473385:hepoxilin synthase