title: Mutations in the fatty acid transport protein 4 gene cause the ichthyosis prematurity syndrome.
abstract: Ichthyosis prematurity syndrome (IPS) is an autosomal-recessive disorder characterized by premature birth and neonatal asphyxia, followed by a lifelong nonscaly ichthyosis with atopic manifestations. Here we show that the gene encoding the fatty acid transport protein 4 (FATP4) is mutated in individuals with IPS. Fibroblasts derived from a patient with IPS show reduced activity of very long-chain fatty acids (VLCFA)-CoA synthetase and a specific reduction in the incorporation of VLCFA into cellular lipids. The human phenotype is consistent with Fatp4 deficiency in mice that is characterized by a severe skin phenotype, a defective permeability barrier function, and perturbed VLCFA metabolism. Our results further emphasize the importance of fatty acid metabolism for normal epidermal barrier function illustrated by deficiency of a member in the FATP family of proteins.
authors.affiliation: Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Klar
authors.forename: Martina
authors.initials: M
authors.lastname: Schweiger
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmerman
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Hans
authors.initials: H
authors.lastname: Törmä
authors.forename: Anders
authors.initials: A
authors.lastname: Vahlquist
authors.forename: Bakar
authors.initials: B
authors.lastname: Bouadjar
authors.forename: Niklas
authors.initials: N
authors.lastname: Dahl
authors.forename: Judith
authors.initials: J
authors.lastname: Fischer
mesh_terms: D001706:Biopsy; D016022:Case-Control Studies; D018389:Codon, Nonsense; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D003241:Consanguinity; D004817:Epidermis / Q000378:metabolism / Q000648:ultrastructure; D050612:Fatty Acid Transport Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018703:Founder Effect; D005808:Genes, Recessive; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D050356:Lipid Metabolism / Q000235:genetics; D009154:Mutation; D011247:Pregnancy; D012873:Skin Diseases, Genetic / Q000235:genetics* / Q000601:surgery / Q000648:ultrastructure; D013577:Syndrome; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D018389:Codon, Nonsense; D050612:Fatty Acid Transport Proteins; C493571:SLC27A4 protein, human; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase