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New mutations in the transglutaminase 1 gene in three families with lamellar ichthyosis
Author(s) -
Cao X.,
Lin Z.,
Yang H.,
Bu D.,
Tu P.,
Chen L.,
Wu H.,
Yang Y.
Publication year - 2009
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/j.1365-2230.2009.03288.x
Subject(s) - lamellar ichthyosis , tissue transglutaminase , ichthyosis , hyperkeratosis , in situ hybridization , mutation , biology , filaggrin , microbiology and biotechnology , genetics , gene , epidermis (zoology) , gene mutation , gene expression , enzyme , immunology , biochemistry , atopic dermatitis , anatomy
Summary 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.