MUTATIONS IN THE GENE FOR TRANSGLUTAMINASE-1 IN AUTOSOMAL RECESSIVE LAMELLAR ICHTHYOSIS

We recently mapped the disease locus for severe autosomal recessive la mellar ichthyosis (LI) to chromosome 14q11 and showed complete linkage with TGM1, the gene encoding transglutaminase 1. We have now identifi ed point mutations in TGM1 in two of the multiplex Li families used in the linkage study. Each nucleotide change causes a non-conservative a mino acid substitution of histidine for one of two adjacent arginine r esidues in exon 3 of the gene (Arg141His, Arg142His). Within the trans glutaminase family, these arginines are invariant within a conserved r egion, distant from the catalytic site of the enzyme. We hypothesize t hat these mutations adversely affect formation of crosslinks essential in production of cornified cell envelopes and a normal stratum corneu m layer of the skin.