Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Eckl, KM; de Juanes, S; Kurtenbach, J; Nätebus, M; Lugassy, J; Oji, V; Traupe, H; Preil, ML; Martínez, F; Smolle, J; Harel, A; Krieg, P; Sprecher, E; Hennies, HC.
Molecular analysis of 250 patients with autosomal recessive congenital ichthyosis: evidence for mutation hotspots in ALOXE3 and allelic heterogeneity in ALOX12B.
J Invest Dermatol. 2009; 129(6):1421-1428
Doi: 10.1038/jid.2008.409
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- Co-Autor*innen der Med Uni Graz
- Smolle Josef
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- Abstract:
- In recent years several new genes for autosomal recessive congenital ichthyosis (ARCI) have been identified. However, little is known about the molecular epidemiology and pathophysiology of this genetically and clinically heterogeneous group of severe disorders of keratinization. ARCI is characterized by intense scaling of the whole integument often associated with erythema. We and others have shown that mutations in ALOX12B and ALOXE3, coding for the lipoxygenases 12R-LOX and eLOX-3 predominantly synthesized in the epidermis, can underlie this rare condition. Here we have surveyed a large group of 250 patients with ARCI for mutations in these two genes. We have identified 11 different previously unreported mutations in ALOX12B and ALOXE3 in 21 ARCI patients from 19 unrelated families and demonstrated that mutations in the two genes are the second most common cause for ARCI in this cohort of patients. Examination of the molecular data revealed allelic heterogeneity for ALOX12B and two mutational hotspots in ALOXE3. Functional analysis of all missense mutations and a splice site mutation demonstrated that complete loss of function of the enzymes underlies the phenotype. Our findings further establish the pivotal role of the 12-lipoxygenase pathway during epidermal differentiation.
- Find related publications in this database (using NLM MeSH Indexing)
- Alleles -
- Arachidonate 12-Lipoxygenase - genetics Arachidonate 12-Lipoxygenase - metabolism
- Cohort Studies -
- DNA Mutational Analysis -
- Exons -
- Genes, Recessive -
- Haplotypes -
- Humans -
- Ichthyosiform Erythroderma, Congenital - genetics
- Lipoxygenase - genetics Lipoxygenase - metabolism
- Models, Genetic -
- Mutation -
- Phenotype -
- Protein Structure, Tertiary -
- Recombinant Proteins - chemistry