In vitreous, the collagen fibrils are composed mainly of type II collagen molecules organised around a core of type XI collagen. In the extracellular matrix, collagen molecules assemble to form heterotypic (composed of more than one collagen type) fibrils. Defects affecting this latter protein, therefore, result in an arthropathy with an unaffected or normal ocular phenotype, whereas defects affecting the former will result in ‘full’ Stickler syndrome affecting both ocular and skeletal organisation. While the α1 chain of type XI collagen is expressed in both ocular and cartilaginous tissue, the α2 chain is predominantly expressed in non-ocular (cartilage) tissue. Type XI is expressed in alternative forms in different tissues. Type IX collagen is also a heterotrimer formed by three different constituent chains encoded by three different genes: COL9A1, COL9A2, and COL9A3. In contrast, type XI collagen is formed as a heterotrimer of three different constituent chains each encoded by three different genes: COL11A1, COL11A2, and COL2A1 (the α(1)II peptide interestingly also forms part of the type XI molecule). From this, it will be seen that type II collagen (a homotrimer) only has a single encoding gene, which is called COL2A1 (COL=collagen 2=Type II, A1=α1 peptide) and whose locus is on the long arm of chromosome 12. In contrast, the genes encoding their constituent protein-building blocks are given Arabic numeral nomenclature, written (for human genes) in upper case. This repeating motif is believed to be essential for correct trimerisation of the polypeptide chains during assembly of the triple helical domain and construction of the mature collagen molecule.Ĭonvention dictates that the collagen types are designated by Roman numerals. In either case, the amino-acid sequence in each of the α chains contributing to the triple helix conforms to a highly conserved repeating triplet sequence, whereby glycine, the smallest amino acid, occupies every third position. Alternatively, they may be different (heterotrimers) as in type XI collagen, which has three different constituent peptide chains. These may be identical (homotrimer) as in type II collagen, constructed from three identical cords of type II collagen polypeptide chains. Mutations affecting the genes encoding all three of these fibrillar collagens are now known to cause Stickler syndrome, but the majority are due to defects in the major structural constituent, type II collagen.Īll collagen molecules include a trimer of 3 α peptide chains. The three principal collagen types found in human vitreous are types II, IX, and XI. ![]() The collagen family is the most abundant protein group found in animals and consists of a heterogeneous group of extracellular glycoproteins incorporating at least one triple helical domain as their signature motif. ![]() The ophthalmologist has a particularly important role in the identification and diagnosis of this latter group. The purpose of this article is, therefore, to bring the ophthalmologist up to date with an overview of the general systemic aspects of the disorder, differential diagnoses, and particularly the novel variations and subgroups with predominantly or exclusively ocular involvement. The last major review was in 1999 3 and research over the last 10 years has brought much new information to light. Initially considered a monogenic disorder (and possibly allelic with Wagner vitreoretinopathy-see below), it has now emerged as the most common manifestation from the spectrum of type II/XI collagenopathies, which also includes spondyloepiphyseal dysplasia congenita (SEDC), Kniest dyplasia, metatropic dysplasia, and achondrogenesis type II. 2 The syndrome is an hereditary connective tissue disorder of fibrillar collagen associated with congenital megalophthalmos, retinal detachment, deafness, cleft palate, Pierre–Robin sequence, joint hypermobility, and premature arthritis. The first report detailing hereditary arthro-ophthalmopathy, or Stickler syndrome as it quickly became known, was in 1965, 1 with a supplementary report 2 years later.
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