A novel missence mutation in the transglutaminase-1 gene in an autosomal recessive congenital ichthyosis patient

Abstract

Autosomal recessive congenital ichthyosis (ARCI) is a rare hereditary disorder of cornification. ARCI is a congenital recessive skin disorder characterized by generalized scaling and hyperkeratosis. Mutations in the transglutaminase-1 (TGM1) gene, which encodes for the epidermal enzyme transglutaminase-1, are one of the causes of ARCI. The transglutaminase 1enzyme, is critical for the assembly of the cornified cell envelope in terminally differentiating keratinocytes. In this study a nine-year old boy who presented with ARCI. The whole exome sequencing WES of transglutaminase-1 gene was investigated. The patient harbored a homozygeous mutation of C.1165T>C transition located in exon8 of TGM1 gene, resulting in the substitution of argenine by serine at amino acid position 389. The parents and one of the sibs were hetrozygeous for the variant and one was homozygeous for wild allele. The mutated allele was not found in controls. This mutation localized in this study correspond to the core catalytic core domain of enzyme, based on provean algorithm, the variant at position level was predicted to decrease TGM1 Enzyme activity by producing an unstable protein.