Transglutaminase1 preferred substrate peptide K5 is an efficient tool in diagnosis of lamellar ichthyosis.

[lamellar ichthyosis]

Lamellar ichthyosis (LI ) is a genetically heterogeneous , severe genodermatosis showing widespread hyperkeratosis of the skin . Transglutaminase 1 (TGase 1 ) deficiency by TGase 1 gene (TGM 1 ) mutations is the most prevalent cause of LI . Screening of TGase 1 deficiency in skin is essential to facilitate the molecular diagnosis of LI . However , cadaverine , the most widely used substrate for TGase activity assay , is not isozyme specific . Recently , a human TGase 1 -specific highly preferred substrate peptide K 5 (pepK 5 ) was generated . To evaluate its potential as a diagnostic tool for LI , we performed pepK 5 labeling of TGase 1 activity in normal human and LI skin . Ca (2 +)-dependent labeling of FITC-pepK 5 was clearly seen in the upper spinous and granular layers of normal human skin where it precisely overlapped with TGase 1 immunostaining . Both specificity and sensitivity of FITC-pepK 5 labeling for TGase 1 activity were higher than those of FITC-cadaverine labeling . FITC-pepK 5 labeling colocalized with involucrin and loricrin immunostaining at cornified cell envelope forming sites . FITC-pepK 5 labeling was negative in LI patients carrying TGM 1 truncation mutations and partially abolished in the other LI patients harboring missense mutations . The present results clearly indicate that pepK 5 is a powerful tool for screening LI patient TGase 1 deficiency when we make molecular diagnosis of LI .