| Summary: | 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: <i>TGM1</i>, <i>ALOX12B</i>, <i>ALOXE3</i>, <i>NIPAL4</i>, <i>CYP4F22</i>, <i>ABCA12</i>, <i>PNPLA1</i>, <i>CERS3</i>, <i>SDR9C7</i>, and <i>SULT2B1</i>. The main focus of this report is the mutational spectrum of the genes <i>ALOX12B</i> and <i>ALOXE3</i>, 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 <i>ALOX12B</i> and 27 pathogenic mutations in <i>ALOXE3</i> 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 <i>ALOX12B</i> and 25 novel mutations in <i>ALOXE3</i>. We investigated the spectrum of mutations in <i>ALOX12B</i> and <i>ALOXE3</i> 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.
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