Self-healing collodion baby: a dynamic phenotype explained by a particular transglutaminase-1 mutation

Spontaneous healing with no or only very mild ichthyosis distinguishes the "self-healing collodion baby" from other congenital ichthyoses. In two self-healing collodion baby siblings with markedly diminished epidermal transglutaminase 1 activity we found the compound heterozygous transglutaminase 1 mutations G278R and D490G. Molecular modeling and biochemical assays of mutant proteins under elevated hydrostatic pressure suggest significantly reduced activity in G278R and a chelation of water molecules in D490G that locks the mutated enzyme in an inactive trans conformation in utero . After birth these water molecules are removed and the enzyme is predicted to isomerize back to a partially active cis form, explaining the dramatic improvement of this skin condition.