A novel ABCA12 pathologic variant identified in an Ecuadorian harlequin ichthyosis patient: A step forward in genotype‐phenotype correlations
Autosomal recessive congenital ichthyoses (ARCI) have been associated with different phenotypes including: harlequin ichthyosis (HI), congenital ichthyosiform erythroderma (CIE), and lamellar ichthyosis (LI). While pathogenic variants in all ARCI genes are associated with LI and CIE phenotypes, the...
| Autores: | , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Servizo Galego de Saúde (SERGAS) |
| Repositorio: | RUNA. Repositorio da Consellería de Sanidade e Sergas |
| OAI Identifier: | oai:runa.sergas.gal:20.500.11940/12841 |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pubmed/?term=30916489 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503032/ http://hdl.handle.net/20.500.11940/12841 |
| Access Level: | acceso abierto |
| Palabra clave: | Ichthyosiform Erythroderma, Congenital Prenatal Diagnosis Research Support, Non-U.S. Gov't Ichthyosis, Lamellar Case Reports Phenotype Codon, Nonsense Mutation, Missense RNA Splice Sites ATP Binding Cassette Transporter 1 fenotipo sitios de empalme del ARN ictiosis lamelar mutación de sentido erróneo transportador de casetes de unión a ATP 1 codón sin sentido ayuda no gubernamental a la investigación, EEUU informes de casos eritrodermia ictiosiforme congénita diagnóstico prenatal Gen ABCA12 Harlequin ichthyosis (HI) Autosomal recessive congenital ichthyoses (ARCI) |
| Sumario: | Autosomal recessive congenital ichthyoses (ARCI) have been associated with different phenotypes including: harlequin ichthyosis (HI), congenital ichthyosiform erythroderma (CIE), and lamellar ichthyosis (LI). While pathogenic variants in all ARCI genes are associated with LI and CIE phenotypes, the unique gene associated with HI is ABCA12. In HI, the most severe ARCI form, pathogenic variants in both ABCA12 gene alleles usually have a severe impact on protein function. The presence of at least one non-truncating variant frequently causes a less severe congenital ichthyosis phenotype (LI and CIE). METHODS: We report the case of a 4-year-old Ecuadorian boy with a severe skin disease. Genetic diagnosis was performed by NGS. In silico predictions were performed using Alamut software v2.11. A review of the literature was carried out to identify all patients carrying ABCA12 splice-site and missense variants, and to explore their genotype-phenotype correlations. RESULTS: Genetic testing revealed a nonsense substitution, p.(Arg2204*), and a new missense variant, p.(Val1927Leu), in the ABCA12 gene. After performing in silico analysis and a comprehensive review of the literature, we conclude that p.(Val1927Leu) affects a well conserved residue which could either disturb the protein function or alter the splicing process, both alternatives could explain the severe phenotype of our patient. CONCLUSION: This case expands the spectrum of ABCA12 reported disease-causing variants which is important to unravel genotype-phenotype correlations and highlights the importance of missense variants in the development of HI. © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. |
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