• allelic and locus heterogeneity;
  • autosomal recessive lamellar ichthyosis;
  • gene mutations;
  • transglutaminase 1

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.

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 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.