Pseudoxanthoma elasticum maps to an 820 kb region of the p13.1 region of chromosome 16. O. Le Saux1, Z. Urban1, H.H.H. Göring2, K. Csiszar1, F.M. Pope3, A. Richard3, I. Pasquali-Ronquetti4, L. Bercovitch4, M.G. Lebwohl4, M. Breuning5, P. van der Berg5, L. Kornet5, N. Doggett4, J. Ott2, P.T.V.M. Paulus5, A.A.B. Bergen5, C.D. Boyd1. 1) Pacific. Biomedical. Research. Center, University of Hawaii, Honolulu, HI; 2) Department of genetics and Development, Columbia University, New York, NY; 3) Institute of Medical genetic, University Hospital of Wales, Cardiff, The United Kingdom; 4) The PXE Consortium and PXE International Inc., Sharon MA; 5) The Netherlands Ophthalmic Research Institute, Amsterdam, The Netherlands.
We have performed linkage analysis on 21 families with Pseudoxanthoma elasticum (PXE) using 10 polymorphic markers located on chromosome 16p13.1. The gene(s) responsible for the PXE phenotype was localized to an 8 cM region of 16p13.1 between markers D16S500 and D16S3041 with a maximum lod score of 8.1 at a recombination fraction of 0.04 for marker D16S3017. The lack of any locus heterogeneity suggests that the major predisposing allele is located in this region. Haplotype studies of a total of 36 PXE families identified several recombinations that further confined the PXE gene(s) to a region between markers D16S3060 and D16S79. This PXE locus was identified within a single YAC clone and several overlapping BAC recombinants. From sequence analysis of the BAC recombinants, it is clear that the distance between markers D16S3060 and D16S79 is about 820 kb and contains a total of 10 genes including 4 pseudogenes. We predict that mutations in one (or more) of the expressed genes in the locus will be responsible for the PXE phenotype in these families.