Human Molecular Genetics Advance Access published online on September 12, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl249
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1 Department of Dermatology, University of Muenster, Von-Esmarch-Str. 58, D-48149, Münster, Germany
* To whom correspondence should be addressed. Bathing suit ichthyosis (BSI) is a striking and unique clinical form of autosomal recessive congenital ichthyosis characterized by pronounced scaling on the bathing suit areas but sparing of the extremities and the central face. Here we report on a series of ten BSI patients. Our genetic, ultrastructural and biochemical investigations show that BSI is caused by transglutaminase-1 (TGase-1) deficiency. Altogether we identified 13 mutations in TGM1 - among them seven novel missense mutations and one novel nonsense mutation. Structural modelling for the Tyr276Asn mutation reveals that the residue is buried in the hydrophobic interior of the enzyme and that the hydroxyl side chain of Tyr276 is exposed to solvent in a cavity of the enzyme. Cryosections of healthy skin areas demonstrated an almost normal TGase activity, in contrast to the affected BSI skin, which only showed a cytoplasmic and clearly reduced TGase-1 activity. The distribution of TGase-1 substrates in the epidermis of affected skin corresponded to the situation in TGase-1 deficiency. Interestingly, the expression of TGase-3 and cathepsin D was reduced. Digital thermography validated a striking correlation between warmer body areas and presence of scaling in patients suggesting a decisive influence of the skin temperature. In situ TGase testing in skin of BSI patients demonstrated a marked decrease of enzyme activity when the temperature was increased from 25°C to 37°C. We conclude that BSI is caused by TGase-1 deficiency and suggest that it is a temperature sensitive phenotype.
Received January 30, 2006
Revised August 31, 2006
Accepted September 7, 2006
Article
Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: evidence for a temperature sensitive phenotype
Vinzenz Oji 1 *, Juliette Mazereeuw Hautier 2, Bijan Ahvazi 3, Ingrid Hausser 4, Karin Aufenvenne 5, Tatjana Walker 5, Natalia Seller 5, Peter M. Steijlen 6, Wolfgang Küster 7, Alain Hovnanian 8, Hans Christian Hennies 9, and Heiko Traupe 5
2 Dermatology Department, Rangueil Hospital, Toulouse, France; University Paul Sabatier, Toulouse, 31400 France
3 X-ray Crystallography Facility/Office of Science and Technology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
4 Department of Dermatology, University of Heidelberg, Heidelberg, Germany
5 Department of Dermatology, University of Muenster, Münster, Germany
6 Department of Dermatology, University of Maastricht, Maastricht, The Netherlands
7 TOMESA Clinic of Dermatology, Bad Salzschlirf, Germany
8 INSERM, U.563, Toulouse, 31300 France; University Paul Sabatier, Toulouse, 31400 France
9 Cologne Center for Genomics, Division of Dermatogenetics, University of Cologne, Cologne, Germany
Vinzenz Oji, E-mail: ojiv{at}uni-muenster.de, ojiv@mednet.uni-muenster.de
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