title: Identification of COL2A1 gene mutations in patients with chondrodysplasias and familial osteoarthritis.
abstract: OBJECTIVE
  To use a recently developed procedure for analysis of blood leukocyte DNA to detect mutations in the gene for type II procollagen (COL2A1) in patients with cartilage diseases ranging from early-onset familial osteoarthritis (OA) to lethal chondrodysplasias.
  
  
  METHODS
  The technique of denaturing gradient gel electrophoresis was used to scan polymerase chain reaction (PCR) products from 45 exons and exon-flanking sequences of the COL2A1 gene in more than 70 patients with cartilage diseases whose severity ranged from mild to lethal. PCR products with abnormal migrations were then sequenced.
  
  
  RESULTS
  Among the 3 patients with lethal hypochondrogenesis who were analyzed, all 3 were found to have a mutation in the COL2A1 gene. Among 17 patients with spondyloepiphyseal or spondyloepimetaphyseal dysplasia, 2 well-defined and 2 probable mutations were found. Among 15 patients with the Wagner-Stickler syndrome, 2 well-defined and 2 probable mutations were found. Among 45 patients with early-onset familial OA, 1 probable mutation was found.
  
  
  CONCLUSIONS
  Using the procedure developed for analysis of the COL2A1 gene, mutations were detected in > 20% of patients with chondrodysplasias and up to 2% of patients with early-onset familial OA. However, these percentages are only minimal estimates because all possible mutations in the gene cannot be detected with this procedure.
authors.affiliation: Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: P
authors.initials: P
authors.lastname: Ritvaniemi
authors.forename: J
authors.initials: J
authors.lastname: Körkkö
authors.forename: J
authors.initials: J
authors.lastname: Bonaventure
authors.forename: M
authors.initials: M
authors.lastname: Vikkula
authors.forename: J
authors.initials: J
authors.lastname: Hyland
authors.forename: P
authors.initials: P
authors.lastname: Paassilta
authors.forename: I
authors.initials: I
authors.lastname: Kaitila
authors.forename: H
authors.initials: H
authors.lastname: Kääriäinen
authors.forename: B P
authors.initials: BP
authors.lastname: Sokolov
authors.forename: M
authors.initials: M
authors.lastname: Hakala
mesh_terms: D002358:Cartilage, Articular / Q000473:pathology; D002806:Chondrodysplasia Punctata / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000032:analysis; D006801:Humans; D007962:Leukocytes / Q000737:chemistry; D009154:Mutation; D010003:Osteoarthritis / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011347:Procollagen / Q000235:genetics*
chemical_list: D011347:Procollagen; D004247:DNA