Type II achondrogenesis-hypochondrogenesis: Identification of abnormal type II collagen

M. Godfrey, D. W. Hollister

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Abstract

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 of coextracted types I and XI collagen chains, type II collagen chains exhibited retarded mobility. Two-dimensional SDS-PAGE revealed extensive overmodification of all type II cyanogen bromide peptides in a pattern consistent with heterozygosity for an abnormal proα1(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.

Original languageEnglish (US)
Pages (from-to)904-913
Number of pages10
JournalAmerican Journal of Human Genetics
Volume43
Issue number6
StatePublished - Dec 1 1988

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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