Whole Exome Sequencing (Wes) Revealed A Novel Mutation in Krt10 Gene Associated With Epidermolytic Hyperkeratosis

Background and aim: epidermolytic hyperkeratosis (ehk), also known as epidermolytic ichthyosis, is a rare and severe form of ichthyosis. this genetic skin disorder becomes apparent at birth or shortly after birth and affects around 1 in 200,000 to 300,000 people. affected individuals may have reddening (erythroderma), scaling, and severe blistering of the skin. ehk is caused by mutations in the krt1 or krt10 genes. genetic defects of these genes can lead to changes in the keratin proteins, preventing them from forming strong, stable intermediate filament networks within cells. ehk can have various inheritance patterns and, very rarely, mutations in the krt10 gene can be inherited in an autosomal recessive manner. in the present study, we aimed to evaluate a patient with a new pathogenic mutation on the krt10 gene, which is associated with ehk.methods: the study is including a 5-year-old symptomatic girl with scaly, dry, and erythematous skin referred to the dr. mohaddes medical genetics laboratory (dmmgl). her parents were first cousins and there were no similar cases in the family. human whole exome enrichment was performed using twist human core exome kit and the library was sequenced on the illumina platform with coverage of 130x and mean on-target coverage of 52x, performed by cegat gmbh, germany. nearly all exons and flanking 10bp were detected and analyzed. detected variations include single point mutations and small indels (within 20bp). detected variations were then validated using sanger sequencing.results: one mutation c.1159c>t(p.q387*; hom) on the krt10 gene has been detected in homozygous status. the detected homozygous nonsense variant in the krt10 gene has not been previously reported for its pathogenicity. however, multiple downstream truncating mutations have reported previously. multiple lines of in silico computational analysis (mutation taster, cadd, etc.) support the deleterious effect of the variant on the gene or gene product(s). the variant is absent in population databases (exac, 1000g and our local database). based on the acmg guideline, thisvariant can be classified as a likely pathogenic variant. we detected this mutation in patient’s parents in heterozygous status.conclusion: the c.1159c>t(p.q387*; hom) mutation on the krt10 gene has a likely pathogenic effect on the keratin 10 protein structure.