title: Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2.
abstract: Lamellar ichthyosis type 2 (LI2) is a rare autosomal recessive skin disorder for which a gene has been localized on chromosome 2q33-35. We report the identification of five missense mutations in the ABCA12 gene in nine families from Africa affected by LI2. The mutations were homozygous in eight consanguineous families and heterozygous in one non-consanguineous family. Four of these mutations are localized in the first ATP-binding domain (nucleotide-binding fold), which is highly conserved in all ABC proteins. The ABCA12 protein belongs to a superfamily of membrane proteins that translocate a variety of substrates across extra- and intracellular membranes. ABCA transporters have been implicated in several autosomal recessive disorders, notably of lipid metabolism. By analogy with ABCA3, a lamellar body membrane protein in lung alveolar type II cells, ABCA12 could function in cellular lipid trafficking in keratinocytes.
authors.affiliation: Centre National de Génotypage, Evry, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lefévre
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Audebert
authors.forename: Florence
authors.initials: F
authors.lastname: Jobard
authors.forename: Bakar
authors.initials: B
authors.lastname: Bouadjar
authors.forename: Hakima
authors.initials: H
authors.lastname: Lakhdar
authors.forename: Omar
authors.initials: O
authors.lastname: Boughdene-Stambouli
authors.forename: Claudine
authors.initials: C
authors.lastname: Blanchet-Bardon
authors.forename: Roland
authors.initials: R
authors.lastname: Heilig
authors.forename: Mario
authors.initials: M
authors.lastname: Foglio
authors.forename: Jean
authors.initials: J
authors.lastname: Weissenbach
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: D044383:Black People; D002478:Cells, Cultured; D002889:Chromosomes, Human, Pair 2; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D015870:Gene Expression; D005808:Genes, Recessive; D008040:Genetic Linkage; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000145:classification / Q000235:genetics*; D015603:Keratinocytes / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D008954:Models, Biological; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D017421:Sequence Analysis
chemical_list: D005819:Genetic Markers; D026901:Membrane Transport Proteins; D012333:RNA, Messenger