Abstract: 【Abstract】 Objective To investigate the genetic etiology of a pedigree with autosomal recessive congenital ichthyosis. Methods Whole-exome sequencing was performed in a collodion baby, and Sanger sequencing was conducted to verify gene mutations. The PolyPhen-2, PROVEAN and Mutation Taster softwares, as well as protein homology modeling methods, were used to predict features of variants; real?time fluorescence?based quantitative PCR and Western blot analysis were performed to analyze the effect of mutations on allelic mRNA and protein expression. Results Whole-exome sequencing and Sanger sequencing confirmed a mutation c.919C>T （p.Arg307Trp） in exon 6 and a mutation c.1019G>A （p.Gly340Glu） in exon 7 of the TGM1 gene in the infant, which were inherited from his mother and father respectively. Bioinformatics analysis suggested that both the two mutations were harmful to protein structures, which were further supported by protein homology modeling. In vitro experiments showed that there was no significant difference in the mRNA expression of the TGM1 gene between the 293T cells transfected with wild-type plasmids and those transfected with mutant plasmids containing the mutation c.919C>T or c.1019G>A （t = 1.97, 1.28, P = 0.12, 0.27, respectively）, but the TGase1 protein expression significantly decreased in the 293T cells transfected with the mutant TGM1 plasmids. Conclusion The mutations c.919C>T and c.1019G>A in the TGM1 gene may be the molecular genetic etiology of severe ichthyosis in the infant, and the missense amino acids encoded by the two mutations may affect the TGase1 protein function by destroying its structure.

Key words: Ichthyosis, Genes, recessive, DNA mutational analysis, TGM1 gene, Collodion baby