Genetic Etiology of Ichthyosis in Turkish Patients: Next-generation Sequencing Identified Seven Novel Mutations

OBJECTIVE: Ichthyosis is a clinically heterogeneous group of genodermatoses characterized by widespread drying and scaling of the skin. It is also a genetically heterogeneous disorder, and 67 genes associated with the disease have been identified to date. However, there are still undiscovered genes causing the disease. METHODS: We investigated 19 Turkish patients from 17 unrelated families using clinical exome sequencing or multigene panel screening. RESULTS: Sixteen likely pathogenic or pathogenic variants were detected in 13 unrelated patients. We identified “variant of unknown significance” alteration in only one patient. Seven novel variants were identified in ABCA12, ALOX12B, and ALOXE3. The most commonly mutated gene was TGM1, followed by ABCA12 and ALOX12B. CONCLUSIONS: Because of the wide genetic variability of ichthyosis, it is difficult to diagnose the disease quickly and definitively. The clinical use of next-generation sequencing (NGS) methodologies is beneficial in the diagnostic approach to ichthyosis and genetic counseling. This study highlights the underlying molecular cause of ichthyosis by determining the mutational spectrum in a cohort of 19 patients. This study is the first and largest research from Turkey using NGS that highlights all ichthyosis subtypes.