A MISSENSE MUTATION IN TYPE-VII COLLAGEN IN 2 AFFECTED SIBLINGS WITH RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA

Recessive dystrophic epidermolysis bullosa is a severe mutilating geno dermatosis. Previous ultrastructural demonstrations of altered anchori ng fibrils, and recent genetic linkage analyses have suggested that ty pe VII collagen, the major component of anchoring fibrils, is a candid ate gene. We have identified a homozygous methionine-to-lysine mutatio n in two affected siblings, while their unaffected mother and half-bro ther are heterozygous carriers. The mutation resides in a highly conse rved region of the C-terminus of type VII collagen, strongly suggestin g that it is the cause of the disease in this family.