FC-15   MUTATIONS IN THE EPIDERMAL LIPOXUGENASE GENES CAUSE AUTOSOMAL RECESSIVE CONGENITAL ICHTHYOSIS IMPACT ON CONGENITAL ICHTHYOSIS HAIR?

KM Eckl, F. André, W. Küster*, E. Seemanová**, HC Hennies. Max-Delbrück-Centre for Molecular Medicine, Berlin, Germany. *TOMESA Fachklinik, Bad Salzschlirf, Germany. **Dept of Clinical Genetics, Charles University, Prague, Czech Republic.

Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of hereditary keratinisation disorders characterised by more or less intensive scaling of the whole integument often associated with erythema. A further characteristic feature is patchy scarring alopecia, also called alopecia ichthyotica. This form of alopecia is different from the hair defects seen in ichthyosis syndromes such as Netherton’s syndrome or trichothiodystrophy. Up to the present, five loci for ARCI have been mapped to human chromosoms 2q33-q35, 14q11.2, 17p13.1, 19p13.1-p13.2, and 19p12-q12. We have identified the locus on 17p13.1 by homozygosity mapping in two consanguineous German and Turkish families. Recently, mutations in two new genes on 17p13.1, ALOX12B and ALOXE3, were identified in ARCI patients. We have analysed more than 100 families with ARCI and identified novel mutations in ALOX12B and ALOXE3. The genes code for the epidermal 12R-lipoxygenase and lipoxygenase-3, respectively, both members of the epidermis-type subclass of mammalian lipoxygenases. The enzymes share the common structure of lipoxygenases with a PLAT/LH2 and a lipoxygenase domain. The enzyme specificity of the epidermistype lipoxygenases, however, has not yet been clarified. Interestingly, these lipoxygenase genes also present strong expression in the hair follicle cells. A role of transglutaminase 1, mutations of which can also underlie ARCI, in maturation of hair cuticle cells has been suggested earlier. These findings imply a role for epidermis-specific lipoxygenases in processes of growth and differentiation of the hair follicle. Further investigations are being performed in order to elucidate the functional consequences of these mutations.