Three novel point mutations in the keratinocyte transglutaminase (TGK) gene in lamellar ichthyosis: significance for mutant transcript level, TGK immunodetection and activity

Détails

ID Serval
serval:BIB_7AF5753FD0CD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Three novel point mutations in the keratinocyte transglutaminase (TGK) gene in lamellar ichthyosis: significance for mutant transcript level, TGK immunodetection and activity
Périodique
European Journal of Human Genetics
Auteur(s)
Petit  E., Huber  M., Rochat  A., Bodemer  C., Teillac-Hamel  D., Muh  J. P., Revuz  J., Barrandon  Y., Lathrop  M., de Prost  Y., Hohl  D., Hovnanian  A.
ISSN
1018-4813 (Print)
Statut éditorial
Publié
Date de publication
08/1997
Volume
5
Numéro
4
Pages
218-28
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jul-Aug
Résumé
We have investigated 8 patients from 7 unrelated families with lamellar ichthyosis (LI) for defects in the keratinocyte transglutaminase (TGK) gene. We have characterized three novel homozygous mutations and a previously reported splice acceptor site mutation. One patient showed a C-to-T change in the binding site for the transcription factor Sp1 within the promoter region. Another patient had a Gly 143-to-Glu mutation in exon 3 and a third patient, affected with a particular form of LI sparing the four limbs, demonstrated a Val382-to-Met mutation within exon 7. These three patients exhibited drastically reduced transglutaminase activity and an absence of detectable TGK polypeptide, as assessed by immunofluorescence and immunoblotting. Northern blot analysis showed that the Sp1 site mutation was associated with profound reduction of TGK transcript levels whereas normal transcript levels were observed for the two missense mutations. We hypothesize that the Sp1 site mutation impairs transcription of the TGK gene, whereas the two missense mutations induce structural changes leading to protein instability. Linkage to TGK was excluded in another family and no evidence for TGK defect was found in 3 other patients. These results further support the involvement of TGK in some patients with LI. They identify a TGK mutation as a cause for non-generalized LI and further delineate the molecular mechanisms underlying TGK deficiency in LI.
Mots-clé
Adult Blotting, Northern Child Female Fluorescent Antibody Technique, Indirect Humans Ichthyosis, Lamellar/enzymology/*genetics Immunoblotting Linkage (Genetics) Male Pedigree *Point Mutation RNA, Messenger/metabolism Staining and Labeling Transglutaminases/analysis/*genetics
Pubmed
Web of science
Création de la notice
25/01/2008 17:36
Dernière modification de la notice
20/08/2019 15:36
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