Type II achondrogenesis-hypochondrogenesis: identification of abnormal type II collagen.
We have extended the study of a mild case of type II achondrogenesis-hypochondrogenesis to include biochemical analyses of cartilage, bone, and the collagens produced by dermal fibroblasts. Type I collagen extracted from bone and types I and III collagen produced by dermal fibroblasts were normal, as was the hexosamine ratio of cartilage proteoglycans. Hyaline cartilage, however, contained approximately equal amounts of types I and II collagen and decreased amounts of type XI collagen. Unlike the normal SDS-PAGE mobility. Two-dimensional SDS-PAGE revealed extensive overmodification of all type II cyanogen bromide peptides in a pattern consistent with heterozygosity for an abnormal pro alpha 1(II) chain which impaired the assembly and/or folding of type II collagen. This interpretation implies that dominant mutations of the COL2A1 gene may cause type II achondrogenesis-hypochondrogenesis. More generally, emerging data implicating defects of type II collagen in the type II achondrogenesis-hypochondrogenesis-spondyloepiphyseal dysplasia congenita spectrum and in the Kniest-Stickler syndrome spectrum suggest that diverse mutations of this gene may be associated with widely differing phenotypic outcome.
Godfrey
M
M
Shriners Hospital for Crippled Children, Portland, OR 97201.
Hollister
D W
DW
D000596:Amino Acids / Q000032:analysis; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006595:Hexosamines / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D010009:Osteochondrodysplasias / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011487:Protein Conformation
D000596:Amino Acids; D006595:Hexosamines; D003094:Collagen