Glycine to serine substitution in the triple helical domain of pro-α1(II) collagen results in a lethal perinatal form of short-limbed dwarfism

H. Vissing, M. D'Alessio, B. Lee, F. Ramirez, M. Godfrey, D. W. Hollister

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Previous biochemical studies on cartilage tissue from a proband with Type II achondrogenesis-hypochondrogenesis (Godfrey, M., and Hillister, D.W. (1988) Am. J. Hum. Genet. 43, 904-913) indicated heterozygosity for a structural abnormality in the triple helical domain of pro-α1(II) collagen. Here we demonstrate that the mutation in the type II procollagen gene is a single base change that converts th codon for glycine (GGC) at amino acid 943 of the α1(II) chain to a codon for serine (AGC). The substitution disrupts the invariant Gly-X-Y structural motif necessary for perfect triple helix formation and leads to extensive overmodification, intracellular retention, and reduced secretion of type II collagen. These findings confirm the proposal that new dominant mutations in the type II procollagen gene may account for some cases of Type II achondrogenesis-hypochondrogenesis. Since recent studies (Lee, B., Vissing, H., Ramirez, F., Rogers, D., and Rimoin, D. (1989) Science 244, 978-980) have identified a dominantly inherited type II procollagen gene deletion in a non-lethal form of skeletal dysplasia, namely spondyloepiphyseal dysplasia, the data more generally demonstrate that different type II procollagen gene mutations eventuate in a wide and diverse spectrum of clinical phenotypes.

Original languageEnglish (US)
Pages (from-to)18265-18267
Number of pages3
JournalJournal of Biological Chemistry
Issue number31
StatePublished - Jan 1 1989


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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