Kannu Peter, Bateman John, Savarirayan Ravi
Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
J Paediatr Child Health. 2012 Feb;48(2):E38-43. doi: 10.1111/j.1440-1754.2010.01979.x. Epub 2011 Feb 18.
COL2A1 mutations give rise to a spectrum of phenotypes predominantly affecting cartilage and bone from the severe disorders that are perinatally lethal to the milder conditions that are recognised in the post-natal period and childhood. The milder chondrodysplasias are characterised by disproportionate short stature, eye abnormalities, cleft palate and hearing loss. It remains poorly recognised that there is significant variability in the disease presentation, with early onset short stature conditions and later onset milder phenotypes. Similarly, it is under-acknowledged that COL2A1 mutations may solely cause joint disease in the absence of the other mentioned phenotypic clues. The underlying hypothesis is that there are novel phenotypes caused by mutations in type II collagen that extend from premature arthritis through to more severe bone dysplasias. The importance of finding a COL2A1 mutation lies in the subsequent ability to accurately assess recurrence risks and offer information regarding disease natural history. Most importantly, it enables at-risk individuals to be identified for implementation of preventative strategies and early ameliorative management of their condition. Such interventions potentially translate into a reduction in health costs associated with musculoskeletal disease.
COL2A1基因突变会导致一系列主要影响软骨和骨骼的表型，从围产期致死的严重疾病到出生后和儿童期才被认识到的较轻病症。较轻的软骨发育异常的特征是身材不成比例矮小、眼部异常、腭裂和听力丧失。人们仍未充分认识到疾病表现存在显著差异，既有早发性身材矮小的情况，也有晚发性较轻表型。同样，人们也未充分认识到COL2A1基因突变在没有其他所述表型线索的情况下可能单独导致关节疾病。潜在的假设是，II型胶原突变会导致新的表型，从早发性关节炎到更严重的骨发育异常。发现COL2A1基因突变的重要性在于随后能够准确评估复发风险，并提供有关疾病自然史的信息。最重要的是，它能够识别出有风险的个体，以便实施预防策略并对其病情进行早期改善管理。此类干预措施有可能降低与肌肉骨骼疾病相关的医疗成本。
