TY - JOUR
T1 - Meta-Analysis of Mutations in ALOX12B or ALOXE3 Identified in a Large Cohort of 224 Patients
AU - Hotz, Alrun
AU - Kopp, Julia
AU - Bourrat, Emmanuelle
AU - Oji, Vinzenz
AU - Komlosi, Katalin
AU - Giehl, Kathrin
AU - Bouadjar, Bakar
AU - Bygum, Anette
AU - Tantcheva-Poor, Iliana
AU - Hellstrom Pigg, Maritta
AU - Has, Cristina
AU - Yang, Zhou
AU - Irvine, Alan D.
AU - Betz, Regina C.
AU - Zambruno, Giovanna
AU - Tadini, Gianluca
AU - Suessmuth, Kira
AU - Gruber, Robert
AU - Schmuth, Matthias
AU - Mazereeuw-Hautier, Juliette
AU - Jonca, Natalie
AU - Guez, Sophie
AU - Brena, Michela
AU - Hernandez-Martin, Angela
AU - van den Akker, Peter
AU - Bolling, Maria C.
AU - Hannula-Jouppi, Katariina
AU - Zimmer, Andreas D.
AU - Alter, Svenja
AU - Vahlquist, Anders
AU - Fischer, Judith
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - ALOX12B
KW - ALOXE3
KW - ARCI
KW - ichthyosis
U2 - 10.3390/genes12010080
DO - 10.3390/genes12010080
M3 - Article
VL - 12
JO - Genes
JF - Genes
SN - 2073-4425
IS - 1
M1 - 80
ER -