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While pathogenic variants in all ARCI genes are associated with LI and CIE phenotypes, the unique gene associated with HI is <jats:italic>ABCA12<\/jats:italic>. In HI, the most severe ARCI form, pathogenic variants in both <jats:italic>ABCA12<\/jats:italic> gene alleles usually have a severe impact on protein function. The presence of at least one non\u2010truncating variant frequently causes a less severe congenital ichthyosis phenotype (LI and CIE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report the case of a 4\u2010year\u2010old 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 <jats:italic>ABCA12<\/jats:italic> splice\u2010site and missense variants, and to explore their genotype\u2010phenotype correlations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetic testing revealed a nonsense substitution, p.(Arg2204*), and a new missense variant, p.(Val1927Leu), in the <jats:italic>ABCA12<\/jats:italic> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This case expands the spectrum of <jats:italic>ABCA12<\/jats:italic> reported disease\u2010causing variants which is important to unravel genotype\u2010phenotype correlations and highlights the importance of missense variants in the development of HI.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.608","type":"journal-article","created":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T21:56:34Z","timestamp":1553723794000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A novel <i>ABCA12<\/i> pathologic variant identified in an Ecuadorian harlequin 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