title: Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1.
abstract: We report the identification of mutations in lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) genes in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17. Linkage disequilibrium analysis of six families affected by NCIE permitted us to reduce a recently reported interval of 8.4 cM on chromosome 17p13.1 to a 600 kb region around the marker D17S1796, which contains LOX genes. LOX products have long been implicated in skin disorders. Two point mutations and one deletion were found in ALOXE3 and three point mutations were found in ALOX12B in these consanguineous families from the Mediterranean basin. ALOXE3 and ALOX12B are two genes which are physically linked and functionally related. They are separated by 38 kb, have one more exon than the other LOX genes and are mainly expressed in epithelial cells including keratinocytes. Although the main substrate(s) of the two enzymes is (are) still unknown, the products of ALOX12B obtained in experimental systems have been demonstrated to be of R-chirality. It seems likely that the product of one of these enzymes may be the substrate of the other, and that they belong to the same metabolic pathway.
authors.affiliation: Centre National de Génotypage, 91057 Evry, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Jobard
authors.forename: Caroline
authors.initials: C
authors.lastname: Lefèvre
authors.forename: Aysen
authors.initials: A
authors.lastname: Karaduman
authors.forename: Claudine
authors.initials: C
authors.lastname: Blanchet-Bardon
authors.forename: Serap
authors.initials: S
authors.lastname: Emre
authors.forename: Jean
authors.initials: J
authors.lastname: Weissenbach
authors.forename: Meral
authors.initials: M
authors.lastname: Ozgüc
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Prud'homme
authors.forename: Judith
authors.initials: J
authors.lastname: Fischer
mesh_terms: D002648:Child; D002675:Child, Preschool; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000235:genetics*; D015810:Linkage Disequilibrium; D008084:Lipoxygenase / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C095864:lipoxygenase 3; D008084:Lipoxygenase