title: Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis.
abstract: We recently mapped the disease locus for severe autosomal recessive lamellar ichthyosis (LI) to chromosome 14q11 and showed complete linkage with TGM1, the gene encoding transglutaminase 1. We have now identified point mutations in TGM1 in two of the multiplex LI families used in the linkage study. Each nucleotide change causes a non-conservative amino acid substitution of histidine for one of two adjacent arginine residues in exon 3 of the gene (Arg141His, Arg142His). Within the transglutaminase family, these arginines are invariant within a conserved region, distant from the catalytic site of the enzyme. We hypothesize that these mutations adversely affect formation of crosslinks essential in production of cornified cell envelopes and a normal stratum corneum layer of the skin.
authors.affiliation: Genetic Studies Section, National Institute of Arthritis and Musculoskeletal and Skin Disease, NIH, Bethesda, Maryland 20892-2757, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Russell
authors.forename: J J
authors.initials: JJ
authors.lastname: DiGiovanna
authors.forename: G R
authors.initials: GR
authors.lastname: Rogers
authors.forename: P M
authors.initials: PM
authors.lastname: Steinert
authors.forename: N
authors.initials: N
authors.lastname: Hashem
authors.forename: J G
authors.initials: JG
authors.lastname: Compton
authors.forename: S J
authors.initials: SJ
authors.lastname: Bale
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D011503:Transglutaminases / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004247:DNA; D011503:Transglutaminases