A LOCUS FOR AUTOSOMAL RECESSIVE PSEUDOXANTHOMA ELASTICUM, WITH PENETRANCE OF VASCULAR SYMPTOMS IN CARRIERS, MAPS TO CHROMOSOME 16P13.1

Pseudoxanthoma elasticum (PXE) is a heritable systemic disorder charac terized by calcification of the elastic Fibers of the connective tissu e. Symptoms are predominantly noted in the eye, the skin, and the card iovascular system, resulting in visual loss, skin lesions, and life-th reatening vascular disease. In this study we combined homozygosity map ping and genome scanning with 374 markers in affected individuals from a PXE family from a genetically isolated population in The Netherland s. Initial homozygosity in two or three patients was found with up to 20 markers, among which D16S292 located in 16p13.1. Upon refined and m ore extensive family screening of the latter region, close linkage wit hout recombination was found with the marker D16S764 (Z(max) = 6.27). Despite clear autosomal recessive inheritance of the ocular symptoms i n PXE, vascular symptoms appear in 40%-50% of the heterozygotes.