A FAMILY WITH STICKLER SYNDROME TYPE-2 HAS A MUTATION IN THE COL11A1 GENE RESULTING IN THE SUBSTITUTION OF GLYCINE-97 BY VALINE IN ALPHA-1(XI) COLLAGEN

Stickler syndrome (hereditary arthro-ophthalmopathy) is the commonest inherited cause of retinal detachment and one of the commonest autosom al dominant connective tissue dysplasias. There is clinical and locus heterogeneity with about two thirds of families linked to the gene enc oding type II procollagen (COL2A1). Families with Sticklers syndrome t ype 1 have a characteristic congenital vitreous anomaly and are linked without recombination to markers at the COL2A1 locus. In contrast fam ilies with the type 2 variety have a different vitreo-retinal phenotyp e and are not linked to the COL2A1 gene. Type XI collagen is a quantit atively minor fibrillar collagen related to type V collagen and associ ated with the more abundant type II collagen fibrils. A mutation in CO L11A2, the gene for alpha 2 (XI) procollagen, has recently been found in a family described as having Stickler syndrome, although there was no ocular involvement. Here we show for the first time that a family w ith the full Type 2 Stickler syndrome including vitreous and retinal a bnormalities is linked to the COL11A1 gene and characterise the mutati on as a Glycine to Valine substitution at position 97 of the triple he lical domain caused by a single base G-->T mutation. These results are the first to provide confirmation that type XI collagen is an importa nt structural component of human vitreous, They also support previous work suggesting that mutations in the genes encoding collagen XI can g ive rise to some manifestations of Stickler syndrome, but of these, on ly mutations in COL11A1 will give the full syndrome including the vitr eo-retinal features.