Evidence for a nonallelic heterogeneity of epidermodysplasia verruciformiswith two susceptibility loci mapped to chromosome regions 2p21-p24 and 17q25

Epidermodysplasia verruciformis is a rare genodermatosis associated with a high risk of skin cancer. This condition is characterized by an abnormal su sceptibility to specific related human papillomavirus genotypes, including the oncogenic HPV5. Epidermodysplasia verruciformis is usually considered a s an autosomal recessive disease. We recently mapped a susceptibility locus for epidermodysplasia verruciformis (EV1) to chromosome 17qter within the 1 cM interval between markers D17S939 and D17S802. We report here the genot yping for 10 microsatellite markers spanning 29 cM around EV1 in two consan guineous epidermodysplasia verruciformis families from Colombia (C2) and Fr ance (F1) comprising five patients and two patients, respectively. Using ho mozygosity mapping, linkage with 17qter markers was observed for family C2 only. Multipoint linkage analysis yielded maximum multipoint LOD-score valu es above 10 between markers D17S1839 and D17S802 encompassing the EV1 locus . A genome-wide search performed in family F1 yielded evidence for linkage between epidermodysplasia verruciformis and the chromosomal 2p marker D2S36 5. Nine additional microsatellite markers spanning 15 cM in this region wer e analyzed. Assuming an autosomal recessive inheritance with a complete pen etrance, the expected maximum two-point LOD-score value of 1.8 was obtained for three markers and multipoint linkage analysis yielded a maximum LOD-sc ore value of 3.51 between markers D2S2144 and D2S392. Haplotype analysis al lowed to map a candidate region for a second epidermodysplasia verruciformi s susceptibility locus (EV2) within the 8 cM interval between markers D2S17 1 and D2S2347 of the 2p21-p24 region. In contrast, linkage with 2p markers was excluded for family C2 and for the three families in which we mapped EV 1 previously. The disclosure of two susceptibility loci for epidermodysplas ia verruciformis provides evidence for a nonallelic heterogeneity in this d isease.