{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T02:21:39Z","timestamp":1792981299564,"version":"4.5.0"},"reference-count":26,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"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>Autosomal recessive congenital ichthyosis (ARCI) is a non-syndromic congenital disorder of cornification characterized by abnormal scaling of the skin. The three major phenotypes are lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. ARCI is caused by biallelic mutations in ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, NIPAL4, PNPLA1, SDR9C7, SULT2B1, and TGM1. The most severe form of ARCI, harlequin ichthyosis, is caused by mutations in ABCA12. Mutations in this gene can also lead to congenital ichthyosiform erythroderma or lamellar ichthyosis. We present a large cohort of 64 patients affected with ARCI carrying biallelic mutations in ABCA12. Our study comprises 34 novel mutations in ABCA12, expanding the mutational spectrum of ABCA12-associated ARCI up to 217 mutations. Within these we found the possible mutational hotspots c.4541G&gt;A, p.(Arg1514His) and c.4139A&gt;G, p.(Asn1380Ser). A correlation of the phenotype with the effect of the genetic mutation on protein function is demonstrated. Loss-of-function mutations on both alleles generally result in harlequin ichthyosis, whereas biallelic missense mutations mainly lead to CIE or LI.<\/jats:p>","DOI":"10.3390\/genes14030717","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T05:53:44Z","timestamp":1678859624000},"page":"717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Mutational Spectrum of the ABCA12 Gene and Genotype\u2013Phenotype Correlation in a Cohort of 64 Patients with Autosomal Recessive Congenital Ichthyosis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2560-3951","authenticated-orcid":false,"given":"Alrun","family":"Hotz","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Center for Cornification Disorders, Freiburg Center for Rare Diseases, Medical Center, University of Freiburg, 79106 Freiburg, Germany"},{"name":"European Reference Networks (ERN Skin), 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Kopp","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira","family":"S\u00fc\u00dfmuth","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Muenster University Medical Center, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6076-9992","authenticated-orcid":false,"given":"Katalin","family":"Komlosi","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Center for Cornification Disorders, Freiburg Center for Rare Diseases, Medical Center, University of Freiburg, 79106 Freiburg, Germany"},{"name":"European Reference Networks (ERN Skin), 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bakar","family":"Bouadjar","sequence":"additional","affiliation":[{"name":"Department of Dermatology, CHU of Bab-El-Oued Algiers, Algiers 16008, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iliana","family":"Tantcheva-Po\u00f3r","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Faculty of Medicine and University Hospital, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maritta","family":"Hellstr\u00f6m Pigg","sequence":"additional","affiliation":[{"name":"Clinical Genetics, Karolinska University Hospital, 171 64 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5024-3623","authenticated-orcid":false,"given":"Regina","family":"Betz","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn, Medical Faculty & University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Giehl","sequence":"additional","affiliation":[{"name":"European Reference Networks (ERN Skin), 75015 Paris, France"},{"name":"Department of Dermatology, Venerology und Allergology, University Hospital of Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Schedel","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Muenster University Medical Center, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Weibel","sequence":"additional","affiliation":[{"name":"Pediatric Skin Center, Dermatology Department, University Children\u2019s Hospital Zurich, 8032 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solveig","family":"Schulz","sequence":"additional","affiliation":[{"name":"Synlab Medical Practice for Human Genetics Jena, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7321-7305","authenticated-orcid":false,"given":"Dora","family":"St\u00f6lzl","sequence":"additional","affiliation":[{"name":"Center for Inflammatory Skin Diseases, Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Tadini","sequence":"additional","affiliation":[{"name":"European Reference Networks (ERN Skin), 75015 Paris, France"},{"name":"Pediatric Dermatology Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca\u2019 Granda\u2014Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emine","family":"Demiral","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Inonu University School of Medicine, 44280 Malatya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Berggard","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Sk\u00e5ne University Hospital, 221 85 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5595-9388","authenticated-orcid":false,"given":"Andreas","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2233-8734","authenticated-orcid":false,"given":"Svenja","family":"Alter","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Center for Cornification Disorders, Freiburg Center for Rare Diseases, Medical Center, University of Freiburg, 79106 Freiburg, Germany"},{"name":"European Reference Networks (ERN Skin), 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8580-8118","authenticated-orcid":false,"given":"Judith","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Center for Cornification Disorders, Freiburg 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