Mutations in ABCC6 cause pseudoxanthoma elasticum


Pseudoxanthoma elasticum (PXE) is a heritable disorder of the connective tissue. PXE patients frequently experience visual field loss and skin lesions, and occasionally cardiovascular complications1,2,3,4. Histopathological findings reveal calcification of the elastic fibres and abnormalities of the collagen fibrils5. Most PXE patients are sporadic, but autosomal recessive and dominant inheritance are also observed6,7. We previously localized the PXE gene to chromosome 16p13.1 (refs 8,9) and constructed a physical map10. Here we describe homozygosity mapping in five PXE families and the detection of deletions or mutations in ABCC6 (formerly MRP6) associated with all genetic forms of PXE in seven patients or families.

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Figure 1: Clinical phenotype, segregation and mutation analysis in a large arPXE pedigree (P-12).
Figure 2: Overview of the positional identification of the PXE gene.
Figure 3: RT–PCR of ABCC6 RNA in various tissues.

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We thank C. Boyd for sharing unpublished data; R.J. Oostra, R. Hennekam, N.T. Tijmes, P. van den Berg, L. Kornet, J.R.M. Cruysberg and F. Steijlen for examination of patients; F. Cremers, C. de Vries and J. Wijnholds for RNA of different tissues; M. Lettink, M.T. van Meegen and D. Schildknegt for technical assistance; and the PXE families for their support. This study was supported by a ANVtVB-grant to A.A.B.B.

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Correspondence to Arthur A.B. Bergen.

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