Premature arthritis is a distinct type II collagen phenotype.
Mutations in the gene encoding type II collagen (COL2A1) give rise to a spectrum of phenotypes predominantly affecting cartilage and bone. These chondrodysplasias are typically characterized by disproportionately short stature, eye abnormalities, cleft palate, and hearing loss. It is less recognized that mutations in COL2A1 can also present as degenerative joint disease in the absence of any other phenotypic clues. We report 2 Australian families presenting with an isolated arthritis phenotype, segregating as a dominant trait affecting both large and small joints, prior to age 30 years. Sequencing of COL2A1 in the propositi revealed 2 sequence changes resulting in glycine substitutions in the triple-helical domain of type II collagen. We review the increasing evidence implicating COL2A1 mutations in individuals presenting with isolated degenerative joint disease, aiming to alert physicians who assess these patients to this possibility. The importance of finding a COL2A1 mutation in such patients lies in the subsequent ability to accurately assess recurrence risks, offer early (including prenatal) diagnosis, and provide information regarding the natural history of the condition. Most importantly, it enables at-risk individuals to be identified for implementation of preventative strategies (i.e., weight loss, joint-friendly exercise programs) and early ameliorative management of their condition.
Murdoch Childrens Research Institute, University of Melbourne, and Genetic Health Services Victoria, Parkville, Melbourne, Australia. kannu@queensu.ca
Peter
P
Kannu
John F
JF
Bateman
Susan
S
Randle
Shannon
S
Cowie
Desiree
D
du Sart
Shaun
S
McGrath
Matthew
M
Edwards
Ravi
R
Savarirayan
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D024043:Collagen Type II / Q000235:genetics*; D019066:Facies; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010003:Osteoarthritis / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D011859:Radiography; D012307:Risk Factors
C499177:COL2A1 protein, human; D024043:Collagen Type II