title: A large kindred of early-onset osteoarthritis of the knee and hip: excluding the link to COL2A1 gene.
abstract: OBJECTIVE
  To characterize a large extended family with early-onset OA of the knee and investigate its associations with the COL2A1 gene.
  
  
  METHODS
  Phenotype assessments were conducted in a six-generation family to identify individuals affected with OA. Short tandem repeat polymorphic (STRP) markers and DNA sequencing were performed to investigate the involvement of the COL2A1 gene in this family.
  
  
  RESULTS
  The kindred affected with OA showed autosomal dominant inheritance. The mean age of onset was 37.3 +/- 19.2, 29.8 +/- 13.7 and 12.0 +/- 7.2 years for generations IV, V and VI, respectively, and 25 +/- 16.1 years for males and 34.3 +/- 15.5 years for females. The height of the affected males was shorter than the unaffected males (155.9 +/- 11.4 vs 164.5 +/- 16.0 cm, P = 0.010). Arm span in the affected males was also significantly shorter than the unaffected males (158.4 +/- 12.5 vs 165.3 +/- 16.7 cm, P = 0.027). However, both height and arm span were not reduced in the affected female OA patients. STRP markers surrounding COL2A1 locus did not show linkage of the COL2A1 locus with the OA. Sequencing of COL2A1 gene revealed three single nucleotide polymorphisms but no mutation was found in the affected patients.
  
  
  CONCLUSIONS
  The COL2A1 was not a susceptibility gene responsible for the OA phenotype in a large extended kindred with familial early-onset OA. The availability of DNA samples will allow genome-wide linkage study to identify the susceptibility locus.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Academia Sinica, Taipei, Taiwan.
authors.forename: Shu-Chi
authors.initials: SC
authors.lastname: Mu
authors.forename: Hwa-Chang
authors.initials: HC
authors.lastname: Liu
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
authors.forename: Ming-Ta Michael
authors.initials: MT
authors.lastname: Lee
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Chuang
authors.forename: Liang-Kuang
authors.initials: LK
authors.lastname: Chen
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002874:Chromosome Mapping; D024043:Collagen Type II / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006621:Hip Joint / Q000000981:diagnostic imaging; D006801:Humans; D007719:Knee Joint / Q000000981:diagnostic imaging; D008297:Male; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000235:genetics*; D015207:Osteoarthritis, Hip / Q000000981:diagnostic imaging / Q000235:genetics; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D017422:Sequence Analysis, DNA
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II