Abstract

Collagen XI is a minor component of articular cartilage collagen fibrils together with collagen IX. They are in close functional relationship with the major cartilage collagen II. Collagen XI has been suggested to play a role in regulating the diameter of collagen II fibrils. Together these collagens form a supportive framework in the extracellular matrix. Besides articular cartilage, these three collagens can also be found in the vitreous body of the eye, the intervertebral disc, the inner ear and in various tissues during embryonic development.

As the major cartilage collagen, collagen II has been studied quite extensively. Several syndromes ranging from lethal to milder ones have been shown to result from collagen II gene defects. Far less is known about defects in genes coding for the minor cartilage collagens, IX and XI. By identifying mutations in the coding genes and observing the resulting phenotypes, the function and importance of these genes start to unravel.

The goal of this study was to provide more information about collagen XI. As a quantatively minor cartilage component, it is a good candidate for mild disease phenotypes. Collagen XI gene mutations have been shown to cause relatively mild phenotypes, such as Stickler and Marshall syndromes and non-syndromic hearing loss.

Seven families with a recessive chondrodysplasia, otospondylomegaepiphyseal dysplasia (OSMED), were analysed for mutations in COL11A2. This study showed that OSMED is typically caused by the absence of the α2(XI) chains. Sixty-two patients with isolated Robin sequence, cleft palate or micrognathia were analysed for COL11A2 gene mutations. Six unique nucleotide changes were found that are likely to associate with the phenotype. The results showed that collagen XI gene defects can play a role in the etiology of oral clefting, but are not common causes of these phenotypes. Altogether 72 unrelated osteoarthrosis (OA) patients and one family with OA were analysed for mutations in genes coding for collagens II, IX and XI. Eighteen percent of them were found to have a unique sequence variation. An association analysis of OA patients failed to reveal any common predisposing alleles in these genes.