title: The aggrecanopathies; an evolving phenotypic spectrum of human genetic skeletal diseases.
abstract: The large chondroitin sulphated proteoglycan aggrecan (ACAN) is the most abundant non-collagenous protein in cartilage and is essential for its structure and function. Mutations in ACAN result in a broad phenotypic spectrum of non-lethal skeletal dysplasias including spondyloepimetaphyseal dysplasia, spondyloepiphyseal dysplasia, familial osteochondritis dissecans and various undefined short stature syndromes associated with accelerated bone maturation. However, very little is currently known about the disease pathways that underlie these aggrecanopathies, although they are likely to be a combination of haploinsufficiency and dominant-negative (neomorphic) mechanisms. This review discusses the known human and animal aggrecanopathies in the context of clinical presentation and potential disease mechanisms.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, NE1 3BZ, UK.
authors.forename: Beth G
authors.initials: BG
authors.lastname: Gibson
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, NE1 3BZ, UK. michael.briggs@newcastle.ac.uk.|International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK. michael.briggs@newcastle.ac.uk.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Briggs
mesh_terms: D053674:Aggrecans / Q000378:metabolism; D001848:Bone Diseases, Developmental / Q000378:metabolism* / Q000473:pathology*; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009154:Mutation / Q000235:genetics; D010009:Osteochondrodysplasias / Q000378:metabolism* / Q000473:pathology*; D010375:Pedigree
chemical_list: D053674:Aggrecans
keywords: Aggrecan; Cartilage; Chondrodysplasia; Osteochondritis dissecans; Skeletal dysplasia