Identification of mutations in the transglutaminase 1 gene in lamellar ichthyosis

Lamellar ichthyosis (LI) is an autosomal recessive disorder of cornificatio n. Mutations in the transglutaminase 1 gene (TGM1) have been identified in several families with this disorder. We analyzed two unrelated families wit h offspring affected with LI. Family 1 included affected monozygotic twins, in which a homozygous G-to-T transversion was identified in exon 6 at amin o acid residue R315L. This mutation was also identified in the unaffected m other. In family 2, which consisted of one affected infant, a T-to-G transv ersion in exon 8 resulted in a change of phenylalanine to valine, F400V, an d a C-to-T transition in exon 4 resulted in a change of proline to leucine, P248L. In this family, the mutation F400V was found in the unaffected fath er, and the mutation P248L was identified in the unaffected mother. These f indings extend the growing body of literature documenting mutations in the TGM1 gene as the molecular basis of certain cases of lamellar ichthyosis.