Mutations in the human type II (COL2A1)
collagen gene appear to be the basis for many skeletal disorders such as
spondyloepiphyseal dysplasia [1], achondrogenesis, Kniest, and Stickler
syndrome. Several of these conditions include early-onset osteoarthritis in
addition to the chondrodysplasia phenotype.
Other collagen genes are also involved
etiologically in the chondrodysplasias, e.g., an autosomal dominant form of
Stickler syndrome, characterized by mild spondyloepiphyseal dysplasia (SED) and
early-onset osteoarthritis, results from a mutation involving the COL11A2 gene
that encodes the α2 (XI) chain of the quantitatively minor fibrillar type XI
collagen.
Multiple
epiphyseal dysplasia in humans involving flattening of the epiphyses,
shortening of endochondral bones, and early-onset osteoarthritis has been
linked to a mutation in type IX collagen, and mice made transgenic for α1 (IX)
mutation have been shown to develop osteoarthritis and intervertebral disc
degeneration prematurely. The Disproportionate micromelia (Dmm) mouse has a
mutation that causes lethal dwarfism in the homozygote and mild dwarfism in the
heterozygote.
