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Meta-Analysis
. 2021 Jan 9;12(1):80.
doi: 10.3390/genes12010080.

Meta-Analysis of Mutations in ALOX12B or ALOXE3 Identified in a Large Cohort of 224 Patients

Alrun Hotz  1 , Julia Kopp  1 , Emmanuelle Bourrat  2 , Vinzenz Oji  3 , Katalin Komlosi  1 , Kathrin Giehl  4 , Bakar Bouadjar  5 , Anette Bygum  6   7   8 , Iliana Tantcheva-Poor  9 , Maritta Hellström Pigg  10 , Cristina Has  11 , Zhou Yang  1   12 , Alan D Irvine  13 , Regina C Betz  14 , Giovanna Zambruno  15 , Gianluca Tadini  16 , Kira Süßmuth  3 , Robert Gruber  17 , Matthias Schmuth  17 , Juliette Mazereeuw-Hautier  18 , Natalie Jonca  19 , Sophie Guez  16 , Michela Brena  16 , Angela Hernandez-Martin  20 , Peter van den Akker  21 , Maria C Bolling  22 , Katariina Hannula-Jouppi  23   24 , Andreas D Zimmer  1 , Svenja Alter  1 , Anders Vahlquist  25 , Judith Fischer  1
Affiliations
Meta-Analysis

Meta-Analysis of Mutations in ALOX12B or ALOXE3 Identified in a Large Cohort of 224 Patients

Alrun Hotz et al. Genes (Basel). .

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: ALOX12B; ALOXE3; ARCI; ichthyosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples of phenotypes of patients carrying mutations in ALOX12B and ALOXE3. (A–C): Patient 72 carries the mutations p.(Arg114Trp) and p.(Tyr383Met) in ALOX12B and shows an erythrodermic skin on the chest (A), scales on the arm and the back (B), and small scales on the popliteal area (C). (D–F): Patient 29 carries the homozygous mutation p.(Glu91*) in ALOXE3 and presented with mild general ichthyosis. Patient 29 shows ichthyosis with knuckle pads on the dorsal sides of the hands (D), fine white scales on the legs (E), and hyperlinearity of the palmar sites of the hands (F).
Figure 2
Figure 2
(A,D): Schematic presentation of the distribution of mutations in ALOX12B and ALOXE3. Red bold: novel mutations. Blue bold: known mutations, found in our cohort. Black, non-bold: known mutations, not found in our cohort. (B,E): frequency of mutated alleles in ALOX12B and ALOXE3. (C,F): frequency of different types of mutations in ALOX12B and ALOXE3.
Figure 2
Figure 2
(A,D): Schematic presentation of the distribution of mutations in ALOX12B and ALOXE3. Red bold: novel mutations. Blue bold: known mutations, found in our cohort. Black, non-bold: known mutations, not found in our cohort. (B,E): frequency of mutated alleles in ALOX12B and ALOXE3. (C,F): frequency of different types of mutations in ALOX12B and ALOXE3.
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