Department of Ophthalmology, Addenbrooke's Hospital, Cambridge, UK.
Am J Med Genet A. 2012 May;158A(5):1204-7. doi: 10.1002/ajmg.a.35303. Epub 2012 Apr 11.
Mutations in COL2A1, the gene for type II-collagen, can result in a wide variety of phenotypes depending upon the nature of the mutation. Dominant negative mutations tend to result in severe and often lethal skeletal dysplasias such as achondrogenesis type 2, Kniest dysplasia, and spondyloepiphyseal dysplasia congenita. Stickler syndrome, a condition characterized by ophthalmological and orofacial features, deafness and arthritis, usually, but not exclusively, results from haploinsufficiency. Overlapping features of all these disorders can also be seen in the same family. Rare reports have demonstrated that phenotypic variability can be explained in some families by somatic mosaicism. Here, we describe five further examples of somatic mosaicism of COL2A1 mutations illustrating the importance of detailed clinical evaluation and molecular testing even in clinically normal parents of affected individuals.
COL2A1 基因突变可导致多种表型，具体表型取决于突变的性质。显性负突变往往导致严重且常致命的骨骼发育不良，如软骨发育不全 2 型、Kniest 发育不良和先天性脊椎骨骺发育不良。Stickler 综合征是一种以眼科和颌面特征、耳聋和关节炎为特征的疾病，通常（但并非排他性）由单倍体不足引起。所有这些疾病的重叠特征也可在同一家庭中看到。罕见的报道表明，在一些家庭中，表型变异性可以通过体细突变解释。在这里，我们描述了 COL2A1 基因突变的体细突变的另外 5 个例子，说明了即使在受影响个体的临床正常父母中，也需要进行详细的临床评估和分子检测。
