A RADIOGRAPHIC, MORPHOLOGIC, BIOCHEMICAL AND MOLECULAR ANALYSIS OF A CASE OF ACHONDROGENESIS TYPE-II RESULTING FROM SUBSTITUTION FOR A GLYCINE RESIDUE (GLY(691)-]ARG) IN THE TYPE-II COLLAGEN TRIMER

The type II colIagenopathies form a continuous spectrum of clinical se verity, ranging from lethal achondrogenesis type II and hypochondrogen esis, through spondyloepiphyseal dysplasia, spondyloepimetaphyseal dys plasia and Kniest dysplasia to the Stickier syndrome and familial prec ocious osteoarthropathy at the mildest end of the spectrum. We have ca rried out a radiographic, morphologic, biochemical and molecular study in a case of achondrogenesis type II. Electron micrographs showed inc lusion bodies of dilated rough endoplasmic reticulum in the chondrocyt es and the presence of sparse collagen fibers in the cartilage matrix. Protein analysis of collagen from cartilage indicated posttranslation al overmodification of the major cyanogen bromide peptides, and sugges ted a mutation near the carboxyl terminus of the type II collagen mole cule. Analysis at the DNA level demonstrated that the phenotype was pr oduced by a single base change (G-->C) that resulted in the substituti on of glycine(691) by arginine in the type II collagen triple helical domain. We confirm previous observations in three cases of hypochondro genesis that glycine substitutions in the alpha 1(II) chain can result in a phenotype at the most severe end of the type II collagenopathy s pectrum.