Spondyloepiphyseal dysplasia and precocious osteoarthritis in a family with an Arg75→Cys mutation in the procollagen type II gene (COL2A1)

Charlene J. Williams, Eileen L. Considine, Robert G. Knowlton, Antonio Reginato, Guillermo Neumann, David Harrison, Paul Buxton, Sergio Jimenez, Darwin J. Prockop

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Abstract

Direct sequencing of polymerase chain reaction (PCR)-amplified genomic DNA from a patient with spondyloepiphyseal dysplasia and precocious osteoarthritis revealed a single-base change in exon 11 of the type II procollagen gene (COL2A1), which produces an Arg→ Cys mutation in one allele. The proband is a member of a large Chilean kindred presenting with chondrodysplasia of the hips, knees, shoulders, elbows, and spine associated with severe, early-onset osteoarthritis. All affected individuals exhibit mildly short stature; in addition, five out of seven affected family members display shortened metacarpals or metatarsals. DNA from affected and unaffected family members was PCR-amplified and analysis of restriction digests of the products determined that the mutation segregated with the disease with a lod score of 2.2 at zero recombination. The mutation, which resides in the triple-helical region of type II procollagen at amino acid position 75, is the second example of an Arg→Cys mutation in the COL2A1 gene in heritable cartilaginous disease and is the first example of a point mutation in the amino terminal region of the α1(II) chain, that results in a spondyloepiphyseal dysplastic phenotype.

Original languageEnglish (US)
Pages (from-to)499-505
Number of pages7
JournalHuman Genetics
Volume92
Issue number5
DOIs
StatePublished - Nov 1993

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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