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: L J Russell, J J DiGiovanna, G R Rogers, P M Steinert, N Hashem, J G Compton, S J Bale
• Journal: Nature genetics (Nat Genet) Vol. 9 Issue 3 Pg. 279-83 (Mar 1995) ISSN: 1061-4036 [Print] United States
• PMID: 7773290 (Publication Type: Comparative Study, Journal Article)

Chemical References

• DNA Primers
• DNA
• Transglutaminases

Topics

• Amino Acid Sequence
• Animals
• Base Sequence
• Chromosome Mapping
• Chromosomes, Human, Pair 14
• Conserved Sequence
• DNA (genetics)
• DNA Primers (genetics)
• Female
• Genes, Recessive
• Genetic Linkage
• Humans
• Ichthyosis, Lamellar (enzymology, genetics)
• Male
• Molecular Sequence Data
• Pedigree
• Point Mutation
• Polymerase Chain Reaction
• Sequence Homology, Amino Acid
• Transglutaminases (genetics)