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.