Diagnosis of autosomal recessive lamellar ichthyosis with mutations in the TGM1 gene.
BACKGROUND
Autosomal recessive lamellar ichthyosis (ARLI) is a clinically and genetically heterogeneous disorder. In many cases, mutations in the transglutaminase 1 gene (TGM1) have been identified, however, other clinically indistinguishable cases have been linked to chromosomes 2, 3 and 19. Previous studies have failed to establish any correlation between clinical characteristics and genetic mutations.


OBJECTIVE
To investigate the molecular basis of ARLI in 10 patients with the typical clinical presentation of the disorder.


METHODS
We performed polymerase chain reaction and direct sequencing-based mutation screening in all of these patients, and TGM1 immunofluorescence microscopy and in vitro enzyme activity assays in selected patients.


RESULTS
Mutation screening revealed 14 mutations, four of which have been previously described. While immunofluorescence microscopy was negative in patients with non-sense mutations or out-of-frame insertions or deletions, the results were variable in cases with mis-sense mutations and in cases with no mutations in the TGM1 gene. In vitro enzyme activity assays gave results consistent with the mutation data.


CONCLUSIONS
Our findings support the importance of mutation screening in the evaluation of ARLI.
Cserhalmi-Friedman
P B
PB
Departments of Dermatology and Genetics and Development, Columbia University, College of Physicians & Surgeons, 630 W 168th Street VC-1526, New York, NY 10032, USA.
Milstone
L M
LM
Christiano
A M
AM
D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008856:Microscopy, Fluorescence; D009154:Mutation; D010375:Pedigree; D011503:Transglutaminases / Q000235:genetics*
D011503:Transglutaminases; C105804:transglutaminase 1