Identification of heterozygote carriers in families with a recessive form of pseudoxanthoma elasticum (PXE)

Skin biopsies of 18 healthy relatives of patients with pseudoxanthoma elast icum (PXE), belonging to six different recessive families, have been examin ed by optical and electron microscopy in order to determine morphologic alt erations potentially useful for the identification of carriers of this gene tic disorder. These morphologic features have been compared with those obse rved in the same tissue areas of eight PXE patients belonging to the same f amilies, with six normal subjects, and to the carrier status of these appar ently unaffected relatives as determined by haplotype analysis using inform ative markers surrounding the locus of the PXE gene on chromosome 16p. The dermis of all the relatives of PXE patients, established by haplotype analy sis to be heterozygote carriers of a mutation in the PXE gene, exhibited se veral alterations very similar, although less severe, to those typical in P XE patients. Alterations were present in the reticular dermis and consisted of irregular-sized collagen bundles and elastic fibers; elastic fibers fra gmented, cribriform, and mineralized; numerous fibroblasts, larger than nor mal, and subendothelial elastin in small vessels. Strikingly, none of these dermal changes were noted in an unaffected relative in one family who was identified as a noncarrier by haplotype analysis. Although many of these al terations are not specific for PXE, the presence of these morphologic chang es in unaffected relatives of PXE patients indicates alterations in skin th at could be diagnostic for carriers of a subclinical phenotype of PXE.