Objectives: 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.