Whole‐exome sequencing for diagnosis of hereditary ichthyosis

• Published in: Journal of the European Academy of Dermatology and Venereology 2018-06, Vol.32 (6), p.1022-1027
• Main Authors: Sitek, J.C., Kulseth, M.A., Rypdal, K.B., Skodje, T., Sheng, Y., Retterstøl, L.
• Format: Article
• Language: English
• ISSN: 0926-9959; 1468-3083
• DOI: 10.1111/jdv.14870

Background Hereditary ichthyosis constitutes a diverse group of cornification disorders. Identification of the molecular cause facilitates optimal patient care. Objective We wanted to estimate the diagnostic yield of applying whole‐exome sequencing (WES) in the routine genetic workup of inherited ichthyosis. Methods During a 3‐year‐period, all ichthyosis patients, except X‐linked and mild vulgar ichthyosis, consecutively admitted to a university hospital clinic were offered WES with subsequent analysis of ichthyosis‐related genes as a first‐line genetic investigation. Clinical and molecular data have been collected retrospectively. Results Genetic variants causative for the ichthyosis were identified in 27 of 34 investigated patients (79.4%). In all, 31 causative mutations across 13 genes were disclosed, including 12 novel variants. TGM1 was the most frequently mutated gene, accounting for 43.7% of patients suffering from autosomal recessive congenital ichthyosis (ARCI). Conclusion Whole‐exome sequencing appears an effective tool in disclosing the molecular cause of patients with hereditary ichthyosis seen in clinical practice and should be considered a first‐tier genetic test in these patients.