Whole exome sequencing is an accurate method for identification of disease causing genes involved in ichthyosis

Ichthyosis is a heterogeneous family of rare genetic skin disorders both in phenotypic presentation which characterized by dry, thickened and scaly skin, and in genetics, displaying with autosomal dominant, autosomal recessive or X-linked recessive inheritance. There are at least 38 mutant genes known to be associated with the ichthyosis phenotypes. Autosomal recessive congenital ichthyosis is a subgroup caused by mutations in 13 different genes, identifying of these mutations require a comprehensive and accurate detection method. Next Generation Sequencing (NGS) is the best technique in this time for disease causing gene detection. In this study, 14 affected consanguineous families in southern part of Iran which referred to Narges Genetics Diagnostic Laboratory since 2014 to 2018 with syndromic and non-syndromic ichthyosis types, were examined for identifying disease causing genes. DNA was extracted from peripheral blood samples and Whole Exome Sequencing (WES) was done using Hiseq Illumina platform. After analysis according to clinical representations and using genetic databases such as ExAC and bioinformatics tools candidate variants were determined and validated by Sanger sequencing. These cases diagnosed as congenital ichthyosis with autosomal recessive inheritance pattern of which PNPLA1, CTSC, ALOX12B, ABCA12, TGM1 and CYP4F22 were causative genes in these cases. WES can be used to validate the diagnosis of the genetic disorders. In complicated conditions which there are overlapping presentations while other molecular testing are cumbersome, time and cost consuming, WES is the most helpful strategy.