Background: Autosomal recessive lamellar ichthyosis (LI) is a severe skin disorder characterized by generalized hyperkeratosis. Gene mutation in transglutaminase 1 (TGM1), which mediates cross-links in the formation of the cell envelope during terminal differentiation of epidermis, has been identified as a cause of LI.
Objectives: To determine mutations of TGM1 gene in three Chinese families with LI.
Methods: The TGM1 gene was sequenced to identify disease-causing mutations in the three families with LI. One of the results was confirmed by using reverse transcriptase PCR and in situ hybridization. An in situ transglutaminase (TGase) 1 assay was performed to estimate TGase 1 activity in the patients' skin.
Results: Four novel mutations of keratinocyte TGase1 (Q203X, D254N, R687H and IVS4 + 1G-->T) were found in the three families. No TGase 1 mRNA was detected in patient skin using RT-PCR and in situ hybridization, and the in situ TGase assay showed that there was no or decreased TGase 1 activity in patient skin.
Conclusions: Our findings suggest that four novel mutations in TGM1 gene result in decrease or absence of TGase activity in the skin and, as a consequence, cause the phenotype of LI.