Czech dysplasia metatarsal type: another type II collagen disorder

Eur J Hum Genet. 2007 Dec;15(12):1269-75. doi: 10.1038/sj.ejhg.5201913. Epub 2007 Aug 29.

Abstract

Czech dysplasia metatarsal type is an autosomal-dominant disorder characterized by an early-onset, progressive spondyloarthropathy with normal stature. Shortness of third and/or fourth toes is a frequently observed clinical feature. Similarities between individuals with this dysplasia and patients with an R275C mutation in the COL2A1 gene, prompted us to analyze the COL2A1 gene in the original families reported with Czech dysplasia. Targeted sequencing of exon 13 of the COL2A1 gene was performed, followed by sequencing of the remaining exons in case the R275C mutation was not identified. We identified the R275C substitution in two of the original patients reported with Czech dysplasia and three additional patients. All affected individuals had a similar phenotype characterized by normal height, spondyloarthropathy, short postaxial toes and absence of ocular and orofacial anomalies. The R275C mutation was excluded in a third patient reported with Czech dysplasia. However, the identification of the Y1391C mutation in this patient with disproportionate short stature made the diagnosis of spondyloperipheral dysplasia (SPD) more probable. The Y1391C mutation is located in the C-propeptide of the procollagen chain and has been reported before in a patient with the Torrance type of lethal platyspondylic skeletal dysplasia (PLSD-T). Our observation of the same Y1391C mutation in an additional unrelated patient with SPD further supports the evidence that PLSD-T and SPD represent a phenotypic continuum. The R275C mutation in the COL2A1 gene causes a specific type II collagen disorder that was recently delineated as Czech dysplasia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Binding Proteins / chemistry
  • Child
  • Collagen Type II / chemistry
  • Collagen Type II / genetics
  • Collagen Type II / metabolism*
  • Czech Republic
  • Foot Deformities, Congenital / diagnostic imaging
  • Foot Deformities, Congenital / pathology*
  • Humans
  • Knee / diagnostic imaging
  • Metatarsal Bones / diagnostic imaging
  • Metatarsal Bones / pathology
  • Mutation / genetics
  • Osteochondrodysplasias / diagnostic imaging
  • Osteochondrodysplasias / pathology
  • Radiography

Substances

  • COL2A1 protein, human
  • Calcium-Binding Proteins
  • Collagen Type II
  • chondrocalcin