title: A glycine to aspartic acid substitution of COL2A1 in a family with the Strudwick variant of spondyloepimetaphyseal dysplasia.
abstract: BACKGROUND
  Spondyloepimetaphyseal dysplasia (SEMD) is one of a clinically heterogeneous group of skeletal disorders, characterized by defective growth and modelling of the spine and long bones. Common clinical features include disproportionate short stature, malformed vertebrae and abnormal epiphyses or metaphyses. Some cases have been associated with mutations in the COL2A1 gene.
  
  
  OBJECTIVE
  To determine whether the autosomal dominant Strudwick-type SEMD in a three-generation family, showing specific phenotypical features such as chest deformity, limb shortening, myopia and early-onset degenerative osteoarthrosis, might be caused by a novel COL2A1 mutation.
  
  
  METHODS
  Genetic testing and clinical examination of family members.
  
  
  METHODS
  Direct sequencing of PCR-amplified genomic DNA from the COL2A1 gene.
  
  
  RESULTS
  A point mutation within exon 20 of the COL2A1 gene was identified that substituted a glycine for an aspartic acid residue at codon 262.
  
  
  CONCLUSIONS
  All previously reported autosomal dominant mutations causing SEMD have substituted an obligate glycine within the triple helix, in particular at codons 292, 304 and 709 in the three reported Strudwick-type patients. Additionally, a recurrent glycine substitution at codon 154 has been identified in two unrelated Finnish cases with radiological features consistent with the Strudwick subtype. Our sixth helical glycine substitution extends the mutational spectrum and genotype/phenotype correlations of Strudwick-type SEMD.
authors.affiliation: Connective Tissue Genetics Group, Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK.
authors.forename: C
authors.initials: C
authors.lastname: Tysoe
authors.forename: J
authors.initials: J
authors.lastname: Saunders
authors.forename: L
authors.initials: L
authors.lastname: White
authors.forename: N
authors.initials: N
authors.lastname: Hills
authors.forename: M
authors.initials: M
authors.lastname: Nicol
authors.forename: G
authors.initials: G
authors.lastname: Evans
authors.forename: T
authors.initials: T
authors.lastname: Cole
authors.forename: S
authors.initials: S
authors.lastname: Chapman
authors.forename: F M
authors.initials: FM
authors.lastname: Pope
mesh_terms: D001224:Aspartic Acid / Q000235:genetics*; D002648:Child; D024043:Collagen Type II / Q000235:genetics*; D000013:Congenital Abnormalities / Q000473:pathology; D004262:DNA Restriction Enzymes / Q000032:analysis; D005091:Exons / Q000235:genetics; D005998:Glycine / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II; D001224:Aspartic Acid; D004262:DNA Restriction Enzymes; D005998:Glycine