Novel Mutations of the Transglutaminase 1 Gene in Lamellar Ichthyosis
| Autor: | Gerry Melino, Eleonora Candi, Joo Heung Lee, Bijan Ahvazi, Jun-Mo Yang, Mi Ook Cho, Cha Hui Lee, Eil Soo Lee, Kozo Yoneda, Peter M. Steinert, Kwang Sung Ahn |
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| Rok vydání: | 2001 |
| Předmět: |
Keratinocytes
Tissue transglutaminase Hyperkeratosis Mutation Missense lamellar ichthyosis mutations transglutaminase gene Dermatology medicine.disease_cause Biochemistry Structure-Activity Relationship medicine Humans transglutaminase 1 gene RNA Messenger Molecular Biology Gene Cells Cultured Skin Genetics chemistry.chemical_classification Mutation Transglutaminases biology Settore BIO/11 Infant Newborn Hydrogen Bonding Exons Cell Biology Lamellar ichthyosis medicine.disease Enzyme assay Dyskeratosis Protein Structure Tertiary Enzyme Amino Acid Substitution chemistry biology.protein Female Ichthyosis Lamellar |
| Zdroj: | Journal of Investigative Dermatology. 117:214-218 |
| ISSN: | 0022-202X |
| DOI: | 10.1046/j.0022-202x.2001.01429.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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