J C Sitek1,2, M A Kulseth3, K B Rypdal3, T Skodje3, Y Sheng3, L Retterstøl3. 1. Department of Dermatology, Oslo University Hospital, Oslo, Norway. 2. Centre for Rare Disorders, Oslo University Hospital, Oslo, Norway. 3. Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Abstract
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.
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 ichthyosispatients, 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.
Authors: Martha Montalván-Suárez; Uxia Saraiva Esperón-Moldes; Laura Rodríguez-Pazos; Andrés Ordóñez-Ugalde; Fernanda Moscoso; Nora Ugalde-Noritz; Luis Santomé; Laura Fachal; Daniel Tettamanti-Miranda; Juan Carlos Ruiz; Manuel Ginarte; Ana Vega Journal: Mol Genet Genomic Med Date: 2019-03-27 Impact factor: 2.183
Authors: Uxia Esperón-Moldes; Manuel Ginarte-Val; Laura Rodríguez-Pazos; Laura Fachal; Ana Martín-Santiago; Asunción Vicente; David Jiménez-Gallo; Encarna Guillén-Navarro; Loreto Martorell Sampol; María Antonia González-Enseñat; Ana Vega Journal: PLoS One Date: 2020-02-18 Impact factor: 3.240