Histological skin changes in heterozygote carriers of mutations in ABCC6, the gene causing pseudoxanthoma elasticum

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Abstract
Pseudoxanthoma elasticum (PXE) is related to mutations in the ABCC6 gene and characterized pathologically by dystrophic and mineralized elastic fibres. Heterozygote carriers of ABCC6 mutations may have a limited PXE phenotype. To compare histological changes in the skin of genotyped siblings from two PXE pedigrees. Mutation analysis of ABCC6 was performed. Skin biopsy samples were stained (orcein) and immunolabelled for elastin, and for vitronectin and bone sialoprotein, which are partially responsible for the mineralization within the elastorrhexic fibres. Results In all individuals mutation analysis of ABCC6 allowed definition of the genotype status, i.e. PXE (n = 2), heterozygote (n = 7) or wild type (n = 2). The study identified three histological phenotypes related to the ABCC6 genotype in siblings from both families. Heterozygote carriers had changes in dermal elastic fibre organization, morphology and labelling midway between those seen in PXE skin and normal skin. Even though the number of individuals studied here is small and precludes any hasty generalization, having a single mutation in the ABCC6 gene seems enough to modify dermal elastic fibres. The relevance of performing a skin biopsy to identify heterozygote carriers in the family of a PXE patient remains to be determined.