Focal Dermal Hypoplasia: Abnormal Growth Characteristics of Skin Fibroblasts in Culture

Abstract

Focal dermal hypoplasia is an inherited disease affecting the skin, bones, ocular and dental structures. Histologically, the skin lesions are characterized by a marked decrease in dermal connective tissue. Fibroblast cultures initiated from both the skin lesions and the unaffected skin from a patient with focal dermal hypoplasia were used to assess the growth characteristics of these cells as well as potential abnormalities in the metabolism of collagen, the major extracellular gene product of skin fibroblasts. Cells from affected skin were characterized by a markedly compromised growth potential with a mean population doubling time twice that of the controls and a final saturation density of one-fifth that of control cultures. Phase contrast microscopy revealed that fibroblasts derived from the skin lesions were strikingly abnormal and characterized by a large granular cytoplasm with cytoplasmic vacuoles. Despite these findings, the rate of collagen synthesis, measured as the formation of [ 3 H]hydroxyproline in relation to DNA and cell protein was undisturbed in focal dermal hypoplasia. Furthermore, the relative synthesis of genetically distinct pro-collagens of type I and III, isolated by DEAE-cellulose chromatography, was unaltered in the affected cell strains. These findings indicate that, although the synthesis of collagen by individual fibroblasts is normal, an abnormality in cell kinetics may have relevance to the absence of collagen and other connective tissue components of the dermis in focal dermal hypoplasia.