The recent paper from Paolo Gasparini’s lab in Trieste;
“Autosomal recessive Stickler syndrome due to a loss of function mutation in the COL9A3 gene”
Now means that loss of function mutations in all three alpha chains of type IX collagen are responsible for autosomal recessive Stickler syndrome.
All these mutations are predicted to produce truncated type IX collagen alpha-chains that are missing the carboxyl-terminal trimerisation domain. Reinhard Fessler’s group previously demonstrated that deletion of the alpha1(IX) chain in mice leads to a complete loss of all type IX collagen due to the inability of the alpha2(IX) and alpha3(IX) chains to form a stable functional triple helix.
It therefore seems likely that loss of function of any one of the type IX collagen alpha chains results in a complete loss of type IX collagen from the cartilage extracellular matrix.
To date no functional analysis of cartilage from patients with recessive Stickler Syndrome has been performed.
However, a recent study published by the Cologne and Melbourne groups has shown that a “Comparative proteomic analysis of normal and collagen IX null mouse cartilage reveals altered extracellular matrix composition and novel components of the collagen IX interactome.”
Moreover, “Ablation of collagen IX and COMP disrupts epiphyseal cartilage architecture” and that there is an “Altered integration of matrilin-3 into cartilage extracellular matrix in the absence of collagen IX”. See Budde et al 2005 and Blumbach et al 2008.
Taken together it is clear that loss of type IX collagen has a profound affect on the composition, organisation and integrity of the cartilage extracellular matrix. These studies are also consistant with our recent paper showing that an “Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures”.