{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T14:36:28Z","timestamp":1775918188446,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T00:00:00Z","timestamp":1708732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Erythrokeratodermia variabilis (EKV) is a rare genodermatosis characterized by well-demarcated erythematous patches and hyperkeratotic plaques. EKV is most often transmitted in an autosomal dominant manner. Until recently, only mutations in connexins such as GJB3 (connexin 31), GJB4 (connexin 30.3), and occasionally GJA1 (connexin 43) were known to cause EKV. In recent years, mutations in other genes have been described as rare causes of EKV, including the genes KDSR, KRT83, and TRPM4. Features of the EKV phenotype can also appear with other genodermatoses: for example, in Netherton syndrome, which hampers correct diagnosis. However, in autosomal recessive congenital ichthyosis (ARCI), an EKV phenotype has rarely been described. Here, we report on seven patients who clinically show a clear EKV phenotype, but in whom molecular genetic analysis revealed biallelic mutations in ABCA12, which is why the patients are classified in the ARCI group. Our study indicates that ARCI should be considered as a differential diagnosis in EKV.<\/jats:p>","DOI":"10.3390\/genes15030288","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T07:51:39Z","timestamp":1708933899000},"page":"288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Erythrokeratodermia Variabilis-like Phenotype in Patients Carrying ABCA12 Mutations"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2560-3951","authenticated-orcid":false,"given":"Alrun","family":"Hotz","sequence":"first","affiliation":[{"name":"European Reference Networks (ERN Skin), 75015 Paris, France"},{"name":"Center for Cornification Disorders, Freiburg Center for Rare Diseases, Medical Center, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"F\u00f6lster-Holst","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venerology and Allergology, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinzenz","family":"Oji","sequence":"additional","affiliation":[{"name":"European Reference Networks (ERN Skin), 75015 Paris, France"},{"name":"Department of Dermatology and Venereology, Muenster University Medical Center, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuelle","family":"Bourrat","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Reference Center for Rare Skin Diseases MAGEC, Saint Louis Hospital AP-HP, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1439-8577","authenticated-orcid":false,"given":"Jorge","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Slaheddine","family":"Marrakchi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, CHU Hedi Chaker, Sfax University, Sfax 3029, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariem","family":"Ennouri","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Functional Genetics, Faculty of Sciences of Sfax, Sfax University, Sfax 3029, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4158-815X","authenticated-orcid":false,"given":"Lotta","family":"Wankner","sequence":"additional","affiliation":[{"name":"European Reference Networks (ERN Skin), 75015 Paris, France"},{"name":"Center for Cornification Disorders, Freiburg Center for Rare Diseases, Medical Center, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6076-9992","authenticated-orcid":false,"given":"Katalin","family":"Komlosi","sequence":"additional","affiliation":[{"name":"European Reference Networks (ERN Skin), 75015 Paris, France"},{"name":"Center for Cornification Disorders, Freiburg Center for Rare Diseases, Medical Center, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2233-8734","authenticated-orcid":false,"given":"Svenja","family":"Alter","sequence":"additional","affiliation":[{"name":"European Reference Networks (ERN Skin), 75015 Paris, France"},{"name":"Center for Cornification Disorders, Freiburg Center for Rare Diseases, Medical Center, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8580-8118","authenticated-orcid":false,"given":"Judith","family":"Fischer","sequence":"additional","affiliation":[{"name":"European Reference Networks (ERN Skin), 75015 Paris, France"},{"name":"Center for Cornification Disorders, Freiburg Center for Rare Diseases, Medical Center, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,24]]},"reference":[{"key":"ref_1","first-page":"255","article-title":"Erythro-et keratodermia variabilis in a mother and a daughter","volume":"6","year":"1925","journal-title":"Acta Derm. Venereol."},{"key":"ref_2","first-page":"493","article-title":"Congenital angelegte symmetrische progressive Erythrokeratodermie","volume":"4","author":"Gottron","year":"1922","journal-title":"Zentralblatt Haut-Geschlechtskrankh."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1046\/j.1525-1470.2002.00085.x","article-title":"Erythrokeratodermia Variabilis with Erythema Gyratum Repens-like Lesions","volume":"19","author":"Landau","year":"2002","journal-title":"Pediatr. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1440-0960.2005.00165.x","article-title":"Erythrokeratodermas: A classification in a state of flux?","volume":"46","author":"Rogers","year":"2005","journal-title":"Australas. J. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"410","DOI":"10.4103\/0019-5154.160499","article-title":"Progressive Symmetric Erythrokeratoderma Having Overlapping Features with Erythrokeratoderma Variabilis and Lesional Hypertrichosis: Is Nomenclature \u201cErythrokeratoderma Variabilis Progressiva\u201d More Appropriate?","volume":"60","author":"Mahajan","year":"2015","journal-title":"Indian J. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1111\/j.1365-2133.2004.05965.x","article-title":"Does progressive symmetric erythrokeratoderma exist?","volume":"150","year":"2004","journal-title":"Br. J. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1093\/hmg\/11.11.1311","article-title":"A mutation in GJB3 is associated with recessive erythrokeratodermia variabilis (EKV) and leads to defective trafficking of the connexin 31 protein","volume":"11","author":"Gottfried","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/j.1365-2230.2010.03986.x","article-title":"Erythrokeratoderma variabilis caused by a recessive mutation in GJB3","volume":"36","author":"Pessach","year":"2011","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/1346-8138.13220","article-title":"Erythrokeratodermia variabilis et progressiva","volume":"43","year":"2016","journal-title":"J. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.ajhg.2017.05.003","article-title":"Mutations in KDSR Cause Recessive Progressive Symmetric Erythrokeratoderma","volume":"100","author":"Boyden","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1136\/jmedgenet-2016-104107","article-title":"Sprit Recessive progressive symmetric erythrokeratoderma results from a homozygous loss-of-function mutation of KRT83 and is allelic with dominant monilethrix","volume":"54","author":"Shah","year":"2017","journal-title":"J. Med. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.jid.2018.10.044","article-title":"Gain-of-Function Mutations in TRPM4 Activation Gate Cause Progressive Symmetric Erythrokeratodermia","volume":"139","author":"Wang","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Charfeddine, C., Laroussi, N., Mkaouar, R., Jouini, R., Khayat, O., Redissi, A., Mosbah, A., Dallali, H., Debbiche, A.C., and Zaouak, A. (2021). Expanding the clinical phenotype associated with NIPAL4 mutation: Study of a Tunisian consanguineous family with erythrokeratodermia variabilis\u2014Like Autosomal Recessive Congenital Ichthyosis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0258777"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Terrinoni, A., Sala, G., Bruno, E., Pitolli, C., Minieri, M., Pieri, M., Gambacurta, A., Campione, E., Belardi, R., and Bernardini, S. (2023). Partial Loss of Function ABCA12 Mutations Generate Reduced Deposition of Glucosyl-Ceramide, Leading to Patchy Ichthyosis and Erythrodermia Resembling Erythrokeratodermia Variabilis et Progressiva (EKVP). Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241813962"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"D988","DOI":"10.1093\/nar\/gkab1049","article-title":"Ensembl 2022","volume":"50","author":"Cunningham","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1093\/bioinformatics\/btp033","article-title":"Jalview Version 2\u2014A multiple sequence alignment editor and analysis workbench","volume":"25","author":"Waterhouse","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","article-title":"ClinVar: Improving access to variant interpretations and supporting evidence","volume":"46","author":"Landrum","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_19","first-page":"405","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Anesth. Analg."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hotz, A., Kopp, J., Bourrat, E., Oji, V., S\u00fc\u00dfmuth, K., Komlosi, K., Bouadjar, B., Tantcheva-Po\u00f3r, I., Hellstr\u00f6m Pigg, M., and Betz, R.C. (2023). Mutational Spectrum of the ABCA12 Gene and Genotype-Phenotype Correlation in a Cohort of 64 Patients with Autosomal Recessive Congenital Ichthyosis. Genes, 14.","DOI":"10.3390\/genes14030717"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ennouri, M., Zimmer, A.D., Bahloul, E., Chaabouni, R., Marrakchi, S., Turki, H., Fakhfakh, F., Bougacha-Elleuch, N., and Fischer, J. (2022). Clinical and genetic investigation of ichthyosis in familial and sporadic cases in south of Tunisia: Genotype\u2013phenotype correlation. BMC Med. Genom., 15.","DOI":"10.1186\/s12920-021-01154-z"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1111\/j.1365-2133.2005.06828.x","article-title":"Erythrokeratoderma variabilis-like ichthyosis in Chanarin-Dorfman syndrome","volume":"153","author":"Pujol","year":"2005","journal-title":"Br. J. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1001\/jamaneurol.2013.6337","article-title":"Expanding the clinical phenotype associated with ELOVL4 mutation: Study of a large French-Canadian family with autosomal dominant spinocerebellar ataxia and erythrokeratodermia","volume":"71","author":"Noreau","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1093\/hmg\/ddg235","article-title":"Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2","volume":"12","author":"Audebert","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1046\/j.1523-1747.2003.12032.x","article-title":"Self-Healing Collodion Baby: A Dynamic Phenotype Explained by a Particular Transglutaminase-1 Mutation","volume":"120","author":"Raghunath","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1093\/hmg\/ddl249","article-title":"Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: Evidence for a temperature-sensitive phenotype","volume":"15","author":"Oji","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/jid.2012.332","article-title":"Targeted sequence capture and high-throughput sequencing in the molecular diagnosis of ichthyosis and other skin diseases","volume":"133","author":"Scott","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1038\/sj.jid.5700455","article-title":"ABCA12 is the major harlequin ichthyosis gene","volume":"126","author":"Thomas","year":"2006","journal-title":"J. Investig. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1111\/ced.12148","article-title":"Non-syndromic autosomal recessive congenital ichthyosis in the Israeli population","volume":"38","author":"Israeli","year":"2013","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1111\/ijd.13568","article-title":"Summary of mutations underlying autosomal recessive congenital ichthyoses (ARCI) in Arabs with four novel mutations in ARCI-related genes from the United Arab Emirates","volume":"56","author":"Bastaki","year":"2017","journal-title":"Int. J. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.1073\/pnas.1909378117","article-title":"Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging","volume":"117","author":"Hou","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/3\/288\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:04:24Z","timestamp":1760105064000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/3\/288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,24]]},"references-count":31,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["genes15030288"],"URL":"https:\/\/doi.org\/10.3390\/genes15030288","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,24]]}}}