This paper describes a new autosomal incomplete dominant dwarfism, disproportionate micromelia, which has been characterized genetically and phenotypically, and the cartilage of homozygotes, and heterozygotes has been examined by histochemical, immunofluorescence and biochemical methods. Homozygotes, which die at birth, are disproportionately short and have cleft palates. The heterozygotes appear normal at birth but beginning at 1 week of age dwarfism is apparent and increases during growth. Histochemical and biochemical analyses of the cartilage rudiments of homozygotes at day 18 of gestation demonstrate that the cartilage growth plate is disorganized and that the matrix components, collagen and proteoglycan, are altered. Total collagen synthesis is reduced by approximately 30% and the amount of type II collagen is greatly reduced. By immunofluorescence staining with collagen antibodies, it appears that type II collagen is located primarily near the cell surface of chondrocytes but is poorly distributed throughout the remainder of the matrix. The amount of proteoglycan in the cartilage matrix is reduced by approximately 70% as determined by chemical analysis of hexosamines and by [35S]sulfate incorporation. Although the proteoglycans synthesized by the mutant are normal in size and in glycosaminoglycan composition, they were more easily extractable from the matrix than were normal cartilage proteoglycans. Heterozygotes had reduced cartilage matrix proteoglycan by histochemical methods, but the organization of the epiphyseal cartilage was not abnormal. These data suggest that a reduced or abnormal cartilage matrix is the cause of the dwarfism.

This content is only available via PDF.