ABNORMAL TRANSGLUTAMINASE-1 EXPRESSION PATTERN IN A SUBSET OF PATIENTS WITH ERYTHRODERMIC AUTOSOMAL RECESSIVE ICHTHYOSIS

An autosomal recessive ichthyosis characterized by collodian membrane at birth followed by generalized skin redness and fine, light-colored scales has been termed nonbullous congenital ichthyosiform erythroderm a (CIE), CIE has often been classified together with the other major f orm of recessive ichthyosis without internal organ involvement, lamell ar ichthyosis, which is characterized by minimal erythema and a coarse r, darker scale pattern, Recently, autosomal recessive ichthyosis has been associated with keratinocyte transglutaminase (TGase1) defects in some patients, This group of diseases, however, is genetically hetero geneous and TGase1 abnormalities in CIE have not been clearly describe d, Therefore we examined TGase1 expression in five patients with CIE a nd three with classic lamellar ichthyosis. Although lamellar ichthyosi s patients displayed no TGase1 expression, an abnormal intracellular a ccumulation of TGase1 was observed in four of five CIE patients, This finding was specific and was not observed in other skin disorders char acterized by erythema and abnormal cornification, including erythroder mic psoriasis, atopic dermatitis, epidermolytic hyperkeratosis, and Ne therton's syndrome. CIE keratinocytes with abnormal TGase1 localizatio n expressed full-length TGase1 mRNA and protein but demonstrated trans glutaminase activity intermediate between normal and the minimal activ ity seen in lamellar ichthyosis patient cells. The abnormal TGase1 exp ression pattern and CIE clinical features were recapitulated in epider mis regenerated in vivo on immune deficient mice from CIE patient kera tinocytes, These studies describe a specific abnormality in TGase1 int rinsic to keratinocytes in a subset of CIE patients and suggest that t his abnormality may be involved in the disordered epidermal differenti ation seen in this disorder.