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 lined to chromosomes 2, 3 and 19. Previous studies have failed to establish any correlation between clinical characteristics and genetic mutations. Objectives: 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 microscope 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 nan-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.