Triallelic Inheritance of TGM1 and ALOXE3 Mutations Associated with Severe Phenotype of Ichtyosis in an Iranian Family - A Case Report

Abstract

Lamellar ichthyosis is one form of congenital autosomal recessive ichthyosis. To date, seven causative genes for ARCI have been identified. To understand further the genetic spectrum of the disease, we analyzed a four-generation Iranian family with ARCI that had observable inheritance. Exome sequencing data for one of the affected individuals with ichthyosis from a consanguineous Iranian family was analyzed. Potential candidate mutations were analyzed in addi-tional family members to determine if the putative mutation segregated with disease status. A novel homozygous mu-tation (p.D414V) in TGM1 and rs3027232 in ALOXE3 gene in heterozygous form were identified which segregated with disease status in the family. Bioinformatic studies with Polyphen-2 and SIFT showed that these variants are dam-aging. We identified a possible triallelic inheritance in this study. Moreover, this paper illustrates how advances in ge-nome sequencing technologies could be utilized to rapidly elucidate the molecular basis of inherited skin diseases which can be caused by mutations in multiple disease genes.