RT Journal Article SR Electronic T1 Precocious osteoarthritis in a family with recurrent COL2A1 mutation. JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP 1133 OP 1136 VO 33 IS 6 A1 Kerri M Carlson A1 Karen M Yamaga A1 Kent A Reinker A1 Yujen E Hsia A1 Clyde Carpenter A1 Lucienne M Abe A1 Andrea K Perry A1 Donald A Person A1 Douglas A Marchuk A1 Ellen M Raney YR 2006 UL http://www.jrheum.org/content/33/6/1133.abstract AB OBJECTIVE: To examine the genotypic and phenotypic characteristics of a Micronesian kindred with autosomal dominant precocious osteoarthritis (OA). METHODS: We reviewed records and radiographs of 3 index patients and their parents, administered questionnaires to 16 additional kindred members, performed whole-genome scans of 24 family members, and sequenced relevant genes from 16 family members. RESULTS: The kindred displayed early onset OA, enlarged epiphyses, platyspondyly, and brachydactyly with dysplastic findings consistent with mild spondyloepiphyseal dysplasia. Genetic analysis revealed an arginine to cysteine substitution at position 75 of the collagen 2A1 gene, a mutation that has been described in 4 other geographically distinct families. The major phenotypic differences among the families were in height (ranging from short to tall) and hearing loss noted in 3 of the 5 families. CONCLUSION: The presence of the COL2A1 Arg75Cys mutation in 5 geographically distinct areas helps to confirm a potential mutational hotspot. The diverse phenotypic spectrum suggests that modifier genes and environmental factors play a role in the expression of this mutation.