title: Clinical correlations of osteoarthritis associated with a single-base mutation (arginine519 to cysteine) in type II procollagen gene. A newly defined pathogenesis.
abstract: OBJECTIVE
  To investigate the occurrence and clinical correlation of the arg519-to-cys mutation in the type II procollagen gene in patients with osteoarthritis (OA).
  
  
  METHODS
  Sixty-six subjects from 7 families with a strong family history of generalized OA and 13 patients with erosive OA were evaluated clinically and radiologically. Blood samples from 58 subjects in the familial OA group and from all 13 patients with erosive OA were obtained for DNA analysis. Exon 31 of COL2A1, which spans residue 519, was amplified by polymerase chain reaction.
  
  
  RESULTS
  The arg519-to-cys mutation was detected in 2 of the 7 families with generalized OA. In these 2 families, the mutation was present in the 2 probands and in 19 other clinically affected family members, as well as in 3 (so-far) clinically unaffected family members (ages 25, 14, and 11 years). It was absent in 18 clinically unaffected members tested. The mutation was associated with a distinctive pattern of early-onset, aggressive, generalized OA with a mild spinal chondrodysplasia. Inheritance was autosomal dominant. No mutation was found in any of the patients with erosive OA.
  
  
  CONCLUSIONS
  The arg519-to-cys mutation defines a new pathogenic factor in generalized OA with characteristic clinical and radiologic features. The demonstration of a mutation in 3 of 8 families with OA studied thus far suggests a significant incidence of genetically related clinical OA.
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, OH.
authors.forename: Y L
authors.initials: YL
authors.lastname: Pun
authors.forename: R W
authors.initials: RW
authors.lastname: Moskowitz
authors.forename: S
authors.initials: S
authors.lastname: Lie
authors.forename: W R
authors.initials: WR
authors.lastname: Sundstrom
authors.forename: S R
authors.initials: SR
authors.lastname: Block
authors.forename: C
authors.initials: C
authors.lastname: McEwen
authors.forename: H J
authors.initials: HJ
authors.lastname: Williams
authors.forename: J F
authors.initials: JF
authors.lastname: Bleasel
authors.forename: D
authors.initials: D
authors.lastname: Holderbaum
authors.forename: T M
authors.initials: TM
authors.lastname: Haqqi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D005260:Female; D005796:Genes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D011347:Procollagen / Q000235:genetics*; D011859:Radiography
chemical_list: D011347:Procollagen