A novel homozygous CERS3 frameshift mutation causing autosomal recessive congenital ichthyosis type 9: A case report.
Keywords:
Autosomal recessive, Ichthyosis, CERS3 mutation , ceramide synthase 3 , genetic dermatologyAbstract
Autosomal recessive congenital ichthyosis (ARCI) is a collection of uncommon keratinization disorders marked by widespread scaling and erythema from birth. CERS3 variants lead to ARCI type 9 (ARCI9) by interfering with ceramide biosynthesis and the formation of the epidermal barrier. We present a 25-year-old male, born as a collodion baby to consanguineous parents, who exhibited lifelong diffuse, plate-like scaling accompanied by mild ectropion. Histopathology revealed compact orthokeratosis accompanied by mild acanthosis. Genetic analysis identified a novel homozygous frameshift variant in CERS3 (NM_001292029.2:c.437del; p.[Ala146Valfs*9]), deemed likely pathogenic according to ACMG criteria. Parental carrier testing was recommended but has not yet been conducted. This case broadens the mutational spectrum of CERS3-related ichthyosis and underscores the necessity of amalgamating clinical, histological and molecular findings for accurate diagnosis. Genetic confirmation facilitates precise counselling, cascade testing and an enhanced comprehension of ceramide pathway deficiencies in ARCI.
References
1. Radner FPW, Marrakchi S, Kirchmeier P, et al. Mutations in CERS3 cause autosomal recessive congenital ichthyosis in humans. PLoS Genet 2013;9:e1003536. doi: 10.1371/journal.pgen.1003536
2. Fischer J, Bourrat E. Genetics of inherited ichthyoses and related diseases. Acta Derm Venereol 2020;100:adv00096. doi: 10.2340/00015555-3432
3. Peña-Corona SI, Gutiérrez-Ruiz SC, Cortés H, et al. Advances in the treatment of autosomal recessive congenital ichthyosis: a look towards the repositioning of drugs. Front Pharmacol 2023;14:1274248. doi: 10.3389/fphar.2023.1274248
4. Youssefian L, Vahidnezhad H, Saeidian AH, et al. Autosomal recessive congenital ichthyosis: CERS3 mutations identified by a next-generation sequencing panel targeting ichthyosis genes. Eur J Hum Genet 2017;25:1282-5. doi: 10.1038/ejhg.2017.137
5. Eckl KM, Tidhar R, Thiele H, et al. Impaired epidermal ceramide synthesis causes autosomal recessive congenital ichthyosis and reveals the importance of ceramide acyl chain length. J Invest Dermatol 2013;133:2202-11. doi: 10.1038/jid.2013.153
6. Yamamoto M, Sassa T, Kyono Y, et al. Comprehensive stratum corneum ceramide profiling reveals reduced acylceramides in ichthyosis patients with CERS3 mutations. J Dermatol 2021;48:447-56. doi: 10.1111/1346-8138.15725
7. Oji V, Tadini G, Akiyama M, et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Soreze 2009. J Am Acad Dermatol 2010;63:607-41. doi: 10.1016/j.jaad.2009.11.020
8. Schmuth M, Gruber R, Elias PM, Williams ML. Ichthyosis update: towards a function-driven model of pathogenesis. J Invest Dermatol 2007;127:2721-38. doi: 10.1038/sj.jid.5701031
9. Alsaif F, Alkuraya FS. Genetic and clinical spectrum of autosomal recessive congenital ichthyosis in Saudi Arabia. Clin Genet 2019;96:275-80. doi: 10.1111/cge.13688
10. Limmer AL, Garza-Mayers AC, Kruse L, et al. The role of next-generation sequencing in the diagnosis of ichthyosis: expanding the genotype–phenotype correlation. Int J Dermatol 2020;59:1080-6. doi: 10.1111/ijd.14963
11. Bourrat E, Fischer J. Autosomal recessive congenital ichthyosis. In: Kang S, Amagai M, Bruckner AL, et al., eds. Fitzpatrick’s Dermatology in General Medicine. 9th ed. New York: McGraw-Hill; 2019.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Hamad Almutlaq, Turki S. Aljuhani, Methal Albayat , Abdullah Ali N Aljalfan, Sarah Albreiki
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.
How to Cite
