Self-Healing Collodion Baby: a Dynamic Phenotype Explained by a Particular Transglutaminase-1 Mutation

Abstract

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.

Revised nomenclature and classification of inherited ichthyoses: Results of the First Ichthyosis Consensus Conference in Sorèze 2009

“…32,42,43,48 The self-healing collodion baby representing approximately 10% of all ARCI cases 36,49 has so far been associated with TGM1 or ALOX12B mutations. 37,44 The recently described acral selfhealing collodion baby, ie, at birth the collodion membrane is strictly localized to the extremities and then resolves, can also be a result of TGM1 mutations. 41 …”

Epidermal barrier formation and recovery in skin disorders

“…One remarkable exception to the continuation of the barrier deficiency observed at birth is the "selfhealing collodion babies," which have an amino acid change in the TGM1 protein at a site that chelates water only at the higher hydrostatic pressure in utero. Molecular models and biochemical assays predict that, in the drier ex utero environment, the mutant protein attains a different conformation and possesses approximately 80% of normal TGM1 activity (29). These infants are a unique example of how specific protein mutations may have a more or less severe effect in the distinct in utero and ex utero environments.…”

A Case Report on Congenital Ichthyosis - Collodion Baby

“…Only 10% of cases eventually develop normal skin. This is known as self-healing collodion baby [7][8][9] . Self-healing collodion baby is caused by compound heterozygous mutations which in utero render the transglutaminase 1 inactive cis form; after delivery, a normal phenotype develops, since in the extrauterine environment the enzyme isomerizes back to its active trans form.…”