Novel mutations of the transglutaminase 1 gene in lamellar ichthyosis

Jun Mo Yang, Kwang Sung Ahn, Mi Ook Cho, Kozo Yoneda, Cha Hui Lee, Joo Heung Lee, Eil Soo Lee, Eleonora Candi, Gerry Melino, Bijan Ahvazi, Peter M. Steinert

Research output: Contribution to journalArticle

Abstract

Lamellar ichthyosis, one form of congenital autosomal recessive ichthyosis, is caused by mutations in the gene (TGM1) encoding the transglutaminase 1 enzyme. Mutations, deletions, or insertion of TGM1 have been reported so far. Here we report that three novel mutations of TGM1, D101V, N288T, and R306W, cause lamellar ichthyosis in two different families. The patient in family LI-KD has N288T and R306W mutations, and the patient in family LI-LK has D101V and R306W mutations. The activity of the transglutaminase 1 enzyme of the patient in family LI-LK was only about 15% of normal. Also, three-dimensional structural prediction analyses revealed that the N288T and R306W mutations, and possibly the D101V mutation, cause misfolding in the central catalytic core domain of the transglutaminase 1 enzyme that would probably result in reduced enzyme activity. Our data suggest that the greatly reduced transglutaminase 1 activities are due to disruptions of the native folding of transglutaminase 1, and that these mutations may play a critical role in the pathology of lamellar ichthyosis.

Original languageEnglish
Pages (from-to)214-218
Number of pages5
JournalJournal of Investigative Dermatology
Volume117
Issue number2
DOIs
Publication statusPublished - 2001

Keywords

  • Lamellar ichthyosis
  • Mutations
  • Transglutaminase 1 gene

ASJC Scopus subject areas

  • Dermatology

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    Yang, J. M., Ahn, K. S., Cho, M. O., Yoneda, K., Lee, C. H., Lee, J. H., Lee, E. S., Candi, E., Melino, G., Ahvazi, B., & Steinert, P. M. (2001). Novel mutations of the transglutaminase 1 gene in lamellar ichthyosis. Journal of Investigative Dermatology, 117(2), 214-218. https://doi.org/10.1046/j.0022-202X.2001.01429.x