A duplication in chromosome 4q35 is associated with hereditary benign intraepithelial dyskeratosis

Hereditary benign intraepithelial dyskeratosis (HBID) is an autosomal domin ant disorder characterized by elevated epithelial plaques on the ocular and oral mucous membranes. It has been reported primarily, but not exclusively , in individuals of American Indian heritage in North Carolina. We have exa mined and obtained DNA on two large families affected by HBID. Using geneti c linkage analysis we have localized the HBID gene to chromosome 4 (4q35) w ith a peak LOD score of 8.97. Molecular analysis of these data reveals that all individuals affected with HBID in both families demonstrate the presen ce of three alleles for two tightly linked markers, D4S1652 and D4S2390, wh ich map to the telomeric region of 4q35. This suggests the presence of a du plication segregating with the disease phenotype that is most likely involv ed in its causation.