Small deletions in the type II collagen triple helix produce Kniest dysplasia

Douglas J. Wilkin, Andrew S. Artz, Sarah South, Ralph S. Lachman, David L. Rimoin, William R. Wilcox, Victor A. McKusick, Constantine A. Stratakis, Clair A. Francomano, Daniel H. Cohn

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Kniest dysplasia is a moderately severe type II collagenopathy, characterized by short trunk and limbs, kyphoscoliosis, midface hypoplasia, severe myopia, and hearing loss. Mutations in the gene that encodes type II collagen (COL2A1), the predominant protein of cartilage, have been identified in a number of individuals with Kniest dysplasia. All but two of these previously described mutations cause in-frame deletions in type II collagen, either by small deletions in the gene or splice site alterations. Furthermore, all but one of these mutations is located between exons 12 and 24 in the COL2A1 gene. We used heteroduplex analysis to identify sequence anomalies in five individuals with Kniest dysplasia. Sequencing of the index patients' genomic DNA identified four new dominant mutations in COL2A1 that result in Kniest dysplasia: a 21bp deletion in exon 16, an 18-bp deletion in exon 19, and 4-bp deletions in the splice donor sites of introns 14 and 20. A previously described 28-bp deletion at the COL2A1 exon 12-intron 12 junction, deleting the splice donor site, was identified in the fifth case. The latter three mutations are predicted to result in exon skipping in the mRNA encoded from the mutant allele. These data suggest that Kniest dysplasia results from shorter type II collagen monomers, and support the hypothesis that alteration of a specific COL2A1 domain, which may span from exons 12 to 24, leads to the Kniest dysplasia phenotype.

Original languageEnglish (US)
Pages (from-to)105-112
Number of pages8
JournalAmerican journal of medical genetics
Issue number2
StatePublished - 1999
Externally publishedYes


  • COL2A1
  • Kniest dysplasia
  • Mutation
  • Type II collagen

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Small deletions in the type II collagen triple helix produce Kniest dysplasia'. Together they form a unique fingerprint.

Cite this