title: Early-onset osteoarthritis linked to the type II procollagen gene. Detailed clinical phenotype and further analyses of the gene.
abstract: OBJECTIVE
  To specify in detail the clinical phenotype in 2 Finnish families demonstrating linkage between the type II procollagen gene (COL2A1) and osteoarthritis (OA). We also reevaluated the linkage and screened the exon sequences of the COL2A1 gene for mutations.
  
  
  METHODS
  We used single-stranded conformation polymorphism and denaturing gradient-gel electrophoresis techniques for the analyses.
  
  
  RESULTS
  The patients' phenotype represented typical, but early-onset, OA. There was no clinical or radiographic evidence of chondrodysplasia. No mutation in the protein-coding regions of the COL2A1 gene could be identified. However, the linkage analysis with a new multiallelic marker resulted in a statistically more significant logarithm of odds (LOD) score than has been reported.
  
  
  CONCLUSIONS
  Familial OA with classic clinical and radiographic findings is tightly linked to the COL2A1 gene. Systematic screening of the 54 exons did not, however, reveal any mutations; this suggests that the mutation may lie in the promoter region or within the introns of this 35-kb gene.
authors.affiliation: Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Vikkula
authors.forename: A
authors.initials: A
authors.lastname: Palotie
authors.forename: P
authors.initials: P
authors.lastname: Ritvaniemi
authors.forename: J
authors.initials: J
authors.lastname: Ott
authors.forename: L
authors.initials: L
authors.lastname: Ala-Kokko
authors.forename: U
authors.initials: U
authors.lastname: Sievers
authors.forename: K
authors.initials: K
authors.lastname: Aho
authors.forename: L
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011347:Procollagen / Q000235:genetics*; D011859:Radiography
chemical_list: D015345:Oligonucleotide Probes; D011347:Procollagen