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.
Raghunath
Michael
M
Department of Dermatology, University Hospital, Münster, Germany.
Hennies
Hans-Christian
HC
Ahvazi
Bijan
B
Vogel
Melanie
M
Reis
Andre
A
Steinert
Peter M
PM
Traupe
Heiko
H
D002675:Child, Preschool; D005260:Female; D006801:Humans; D007057:Ichthyosis / Q000235:genetics* / Q000473:pathology; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000235:genetics* / Q000473:pathology; D008956:Models, Chemical; D010641:Phenotype; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D012867:Skin / Q000201:enzymology* / Q000473:pathology; D011503:Transglutaminases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D011503:Transglutaminases; C105804:transglutaminase 1