Novel mutations of TGM1 in a child with congenital ichthyosiform erythroderma.

We report novel mutations in the transglutaminase (TGase) 1 gene (TGM1) in a Japanese boy with non-bullous congenital ichthyosiform erythroderma (NBCIE). The patient showed fine, grey or light-brown scales on an erythematous skin. An in situ TGase activity assay detected markedly reduced TGase activity in the patient's epidermis. Electron microscopy revealed incomplete thickening of the cornified cell envelope during keratinization in the epidermis. Sequencing of the entire exons and exon-intron borders of TGM1 revealed that the proband was a compound heterozygote for two novel mutations, 9008delA and R388H. In lamellar ichthyosis, most previously reported TGM1 mutations have been located in the central core domain or upstream of the TGase 1 molecule. In the present NBCIE patient, the frameshift mutation 9008delA resulting in a premature termination codon at the tail of the TGase 1 peptide was in the beta-barrel 2 domain (C-terminal end domain) of the peptide, far from the active sites of the TGase 1 molecule, and the mis-sense mutation R388H was in the core domain.