Early-Onset Osteoarthritis Linked to the Type II Procollagen Gene.
Detailed Clinical Phenotype and Further Analyses of the Gene
M Vikkula, A. Palotie, P. Ritvaniemi, J. Ott, L. Ala-Kokko ,
U. Sievers , K. Aho , L. Peltonen
Arthritis & Rheumatism , 36(3), 401--409 (1993 Mar)
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.
CONCLUSION. 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.
