Genes (Jan 2021)
Meta-Analysis of Mutations in <i>ALOX12B</i> or <i>ALOXE3</i> Identified in a Large Cohort of 224 Patients
- Alrun Hotz,
- Julia Kopp,
- Emmanuelle Bourrat,
- Vinzenz Oji,
- Katalin Komlosi,
- Kathrin Giehl,
- Bakar Bouadjar,
- Anette Bygum,
- Iliana Tantcheva-Poor,
- Maritta Hellström Pigg,
- Cristina Has,
- Zhou Yang,
- Alan D. Irvine,
- Regina C. Betz,
- Giovanna Zambruno,
- Gianluca Tadini,
- Kira Süßmuth,
- Robert Gruber,
- Matthias Schmuth,
- Juliette Mazereeuw-Hautier,
- Natalie Jonca,
- Sophie Guez,
- Michela Brena,
- Angela Hernandez-Martin,
- Peter van den Akker,
- Maria C. Bolling,
- Katariina Hannula-Jouppi,
- Andreas D. Zimmer,
- Svenja Alter,
- Anders Vahlquist,
- Judith Fischer
Affiliations
- Alrun Hotz
- Institute of Human Genetics, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
- Julia Kopp
- Institute of Human Genetics, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
- Emmanuelle Bourrat
- Department of Dermatology, Reference Center for Rare Skin Diseases MAGEC, Saint Louis Hospital AP-HP, 75010 Paris, France
- Vinzenz Oji
- Department of Dermatology and Venereology, Münster University Medical Center, 48149 Münster, Germany
- Katalin Komlosi
- Institute of Human Genetics, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
- Kathrin Giehl
- Department of Dermatology and Allergy, University of Munich LMU, 80337 Munich, Germany
- Bakar Bouadjar
- Department of Dermatology, CHU of Bab-El-Oued Algiers, Algiers 16008, Algeria
- Anette Bygum
- Department of Dermatology, Odense University Hospital, 5000 Odense, Denmark
- Iliana Tantcheva-Poor
- Department of Dermatology, University of Cologne, 50937 Cologne, Germany
- Maritta Hellström Pigg
- Department of Clinical Genetics, Karolinska University Hospital, 17176 Stockholm, Sweden
- Cristina Has
- Department of Dermatology, Medical Center-University of Freiburg, University of Freiburg, 79104 Freiburg, Germany
- Zhou Yang
- Institute of Human Genetics, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
- Alan D. Irvine
- Dermatology, Children’s Health Ireland and Clinical Medicine, Trinity College Dublin, D12 N512 Dublin, Ireland
- Regina C. Betz
- Institute of Human Genetics, School of Medicine & University Hospital Bonn, University of Bonn, 53127 Bonn, Germany
- Giovanna Zambruno
- Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
- Gianluca Tadini
- Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UOSD Pediatria ad Alta Intensità di Cura, 20122 Milan, Italy
- Kira Süßmuth
- Department of Dermatology and Venereology, Münster University Medical Center, 48149 Münster, Germany
- Robert Gruber
- Department of Dermatology, Venereology and Allergy, Medical University of Innsbruck, 6020 Innsbruck, Austria
- Matthias Schmuth
- Department of Dermatology, Venereology and Allergy, Medical University of Innsbruck, 6020 Innsbruck, Austria
- Juliette Mazereeuw-Hautier
- Reference Center for Rare Skin Diseases, Dermatology Department, CHU Larrey, Université Paul Sabatier, 31000 Toulouse, France
- Natalie Jonca
- Department of Epidermis Differentiation and Rheumatoid Autoimmunity, UMR 1056 Inserm University Toulouse, Place du Dr Baylac, Hôpital Purpan, 31059 Toulouse, France
- Sophie Guez
- Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UOSD Pediatria ad Alta Intensità di Cura, 20122 Milan, Italy
- Michela Brena
- Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UOSD Pediatria ad Alta Intensità di Cura, 20122 Milan, Italy
- Angela Hernandez-Martin
- Department of Dermatology, Hospital Infantil Niño Jesús, 28009 Madrid, Spain
- Peter van den Akker
- Department of Genetics, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands
- Maria C. Bolling
- Center for Blistering Diseases, Department of Dermatology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands
- Katariina Hannula-Jouppi
- ERN-Skin Center, Department of Dermatology and Allergology, University of Helsinki and Helsinki University Central Hospital, HUS, 00029 Helsinki, Finland
- Andreas D. Zimmer
- Institute of Human Genetics, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
- Svenja Alter
- Institute of Human Genetics, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
- Anders Vahlquist
- Department of Medical Sciences/Dermatology, Uppsala University, SE-751 85 Uppsala, Sweden
- Judith Fischer
- Institute of Human Genetics, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
- DOI
- https://doi.org/10.3390/genes12010080
- Journal volume & issue
-
Vol. 12,
no. 1
p. 80
Abstract
The autosomal recessive congenital ichthyoses (ARCI) are a nonsyndromic group of cornification disorders that includes lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. To date mutations in ten genes have been identified to cause ARCI: TGM1, ALOX12B, ALOXE3, NIPAL4, CYP4F22, ABCA12, PNPLA1, CERS3, SDR9C7, and SULT2B1. The main focus of this report is the mutational spectrum of the genes ALOX12B and ALOXE3, which encode the epidermal lipoxygenases arachidonate 12-lipoxygenase, i.e., 12R type (12R-LOX), and the epidermis-type lipoxygenase-3 (eLOX3), respectively. Deficiency of 12R-LOX and eLOX3 disrupts the epidermal barrier function and leads to an abnormal epidermal differentiation. The type and the position of the mutations may influence the ARCI phenotype; most patients present with a mild erythrodermic ichthyosis, and only few individuals show severe erythroderma. To date, 88 pathogenic mutations in ALOX12B and 27 pathogenic mutations in ALOXE3 have been reported in the literature. Here, we presented a large cohort of 224 genetically characterized ARCI patients who carried mutations in these genes. We added 74 novel mutations in ALOX12B and 25 novel mutations in ALOXE3. We investigated the spectrum of mutations in ALOX12B and ALOXE3 in our cohort and additionally in the published mutations, the distribution of these mutations within the gene and gene domains, and potential hotspots and recurrent mutations.
Keywords