Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: evidence for a temperature-sensitive phenotype.
Bathing suit ichthyosis (BSI) is a striking and unique clinical form of autosomal recessive congenital ichthyosis characterized by pronounced scaling on the bathing suit areas but sparing of the extremities and the central face. Here we report on a series of 10 BSI patients. Our genetic, ultrastructural and biochemical investigations show that BSI is caused by transglutaminase-1 (TGase-1) deficiency. Altogether, we identified 13 mutations in TGM1-among them seven novel missense mutations and one novel nonsense mutation. Structural modeling for the Tyr276Asn mutation reveals that the residue is buried in the hydrophobic interior of the enzyme and that the hydroxyl side chain of Tyr276 is exposed to solvent in a cavity of the enzyme. Cryosections of healthy skin areas demonstrated an almost normal TGase activity, in contrast to the affected BSI skin, which only showed a cytoplasmic and clearly reduced TGase-1 activity. The distribution of TGase-1 substrates in the epidermis of affected skin corresponded to the situation in TGase-1 deficiency. Interestingly, the expression of TGase-3 and cathepsin D was reduced. Digital thermography validated a striking correlation between warmer body areas and presence of scaling in patients suggesting a decisive influence of the skin temperature. In situ TGase testing in skin of BSI patients demonstrated a marked decrease of enzyme activity when the temperature was increased from 25 to 37 degrees C. We conclude that BSI is caused by TGase-1 deficiency and suggest that it is a temperature-sensitive phenotype.
Oji
Vinzenz
V
Department of Dermatology, University of Muenster, Von-Esmarch-Str. 58 D-48149, Münster, Germany. ojiv@mednet.uni-muenster.de
Hautier
Juliette Mazereeuw
JM
Ahvazi
Bijan
B
Hausser
Ingrid
I
Aufenvenne
Karin
K
Walker
Tatjana
T
Seller
Natalia
N
Steijlen
Peter M
PM
Küster
Wolfgang
W
Hovnanian
Alain
A
Hennies
Hans Christian
HC
Traupe
Heiko
H
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D018389:Codon, Nonsense; D005260:Female; D006801:Humans; D007057:Ichthyosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D007223:Infant; D008297:Male; D008958:Models, Molecular; D020125:Mutation, Missense; D010641:Phenotype; D017422:Sequence Analysis, DNA; D012867:Skin / Q000201:enzymology / Q000473:pathology; D013696:Temperature; D011503:Transglutaminases / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism
D018389:Codon, Nonsense; D011503:Transglutaminases; C105804:transglutaminase 1