title: Diagnosis of autosomal recessive lamellar ichthyosis with mutations in the TGM1 gene.
abstract: 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.
authors: Departments of Dermatology and Genetics and Development, Columbia University, College of Physicians & Surgeons, 630 W 168th Street VC-1526, New York, NY 10032, USA.
authors: P B
authors: PB
authors: Cserhalmi-Friedman
authors: L M
authors: LM
authors: Milstone
authors: A M
authors: AM
authors: Christiano
mesh_terms: 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*
chemical_list: D011503:Transglutaminases; C105804:transglutaminase 1